Hypoxia-inducible factor 1, alpha subunit is a basic helix-loop-helix transcription factor that is regulated by OXYGEN availability and is targeted for degradation by VHL TUMOR SUPPRESSOR PROTEIN.
A basic helix-loop-helix transcription factor that plays a role in APOPTOSIS. It is composed of two subunits: ARYL HYDROCARBON RECEPTOR NUCLEAR TRANSLOCATOR and HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT.
A condition of decreased oxygen content at the cellular level.
An element with atomic symbol O, atomic number 8, and atomic weight [15.99903; 15.99977]. It is the most abundant element on earth and essential for respiration.
Relatively complete absence of oxygen in one or more tissues.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
A mixed-function oxygenase that catalyzes the hydroxylation of a prolyl-glycyl containing peptide, usually in PROTOCOLLAGEN, to a hydroxyprolylglycyl-containing-peptide. The enzyme utilizes molecular OXYGEN with a concomitant oxidative decarboxylation of 2-oxoglutarate to SUCCINATE. The enzyme occurs as a tetramer of two alpha and two beta subunits. The beta subunit of procollagen-proline dioxygenase is identical to the enzyme PROTEIN DISULFIDE-ISOMERASES.
A family of DNA-binding transcription factors that contain a basic HELIX-LOOP-HELIX MOTIF.
Recurring supersecondary structures characterized by 20 amino acids folding into two alpha helices connected by a non-helical "loop" segment. They are found in many sequence-specific DNA-BINDING PROTEINS and in CALCIUM-BINDING PROTEINS.
A transcription factor that takes part in WNT signaling pathway where it may play a role in the differentiation of KERATINOCYTES. The transcriptional activity of this protein is regulated via its interaction with BETA CATENIN.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
A negative regulator of BASIC HELIX-LOOP-HELIX TRANSCRIPTION FACTORS that blocks activation of CYCLIN-DEPENDENT KINASE INHIBITOR P16 and is de-regulated in a variety of NEOPLASMS.
Lists of words, usually in alphabetical order, giving information about form, pronunciation, etymology, grammar, and meaning.
Dioxygenase enzymes that specifically hydroxylate a PROLINE residue on the HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT. They are OXYGEN-dependent enzymes that play an important role in mediating cellular adaptive responses to HYPOXIA.
Software used to locate data or information stored in machine-readable form locally or at a distance such as an INTERNET site.
Databases devoted to knowledge about specific genes and gene products.
The complete genetic complement contained in the DNA of a set of CHROMOSOMES in a HUMAN. The length of the human genome is about 3 billion base pairs.
Multifunctional growth factor which regulates both cell growth and cell motility. It exerts a strong mitogenic effect on hepatocytes and primary epithelial cells. Its receptor is PROTO-ONCOGENE PROTEINS C-MET.
Precursor of plasmin (FIBRINOLYSIN). It is a single-chain beta-globulin of molecular weight 80-90,000 found mostly in association with fibrinogen in plasma; plasminogen activators change it to fibrinolysin. It is used in wound debriding and has been investigated as a thrombolytic agent.
A heterogeneous group of proteolytic enzymes that convert PLASMINOGEN to FIBRINOLYSIN. They are concentrated in the lysosomes of most cells and in the vascular endothelium, particularly in the vessels of the microcirculation.
A proteolytic enzyme that converts PLASMINOGEN to FIBRINOLYSIN where the preferential cleavage is between ARGININE and VALINE. It was isolated originally from human URINE, but is found in most tissues of most VERTEBRATES.
Cell surface protein-tyrosine kinase receptors for HEPATOCYTE GROWTH FACTOR. They consist of an extracellular alpha chain which is disulfide-linked to the transmembrane beta chain. The cytoplasmic portion contains the catalytic domain and sites critical for the regulation of kinase activity. Mutations of the gene for PROTO-ONCOGENE PROTEINS C-MET are associated with papillary renal carcinoma and other neoplasia.
A product of the lysis of plasminogen (profibrinolysin) by PLASMINOGEN activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins.
An extracellular receptor specific for UROKINASE-TYPE PLASMINOGEN ACTIVATOR. It is attached to the cell membrane via a GLYCOSYLPHOSPHATIDYLINOSITOL LINKAGE and plays a role in the co-localization of urokinase-type plasminogen activator with PLASMINOGEN.
Recombinases that insert exogenous DNA into the host genome. Examples include proteins encoded by the POL GENE of RETROVIRIDAE and also by temperate BACTERIOPHAGES, the best known being BACTERIOPHAGE LAMBDA.
The production of red blood cells (ERYTHROCYTES). In humans, erythrocytes are produced by the YOLK SAC in the first trimester; by the liver in the second trimester; by the BONE MARROW in the third trimester and after birth. In normal individuals, the erythrocyte count in the peripheral blood remains relatively constant implying a balance between the rate of erythrocyte production and rate of destruction.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
A ubiquitin-protein ligase that mediates OXYGEN-dependent polyubiquitination of HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT. It is inactivated in VON HIPPEL-LINDAU SYNDROME.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
Cell growth support structures composed of BIOCOMPATIBLE MATERIALS. They are specially designed solid support matrices for cell attachment in TISSUE ENGINEERING and GUIDED TISSUE REGENERATION uses.
Polymers of organic acids and alcohols, with ester linkages--usually polyethylene terephthalate; can be cured into hard plastic, films or tapes, or fibers which can be woven into fabrics, meshes or velours.
Generating tissue in vitro for clinical applications, such as replacing wounded tissues or impaired organs. The use of TISSUE SCAFFOLDING enables the generation of complex multi-layered tissues and tissue structures.
Synthetic or natural materials, other than DRUGS, that are used to replace or repair any body TISSUES or bodily function.
The process of bone formation. Histogenesis of bone including ossification.
Cell-surface molecules that exhibit lineage-restricted patterns of expression during EMBRYONIC DEVELOPMENT. The antigens are useful markers in the identification of EMBRYONIC STEM CELLS.
Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., BIOPOLYMERS; PLASTICS).
The addition of descriptive information about the function or structure of a molecular sequence to its MOLECULAR SEQUENCE DATA record.
The genetic complement of an organism, including all of its GENES, as represented in its DNA, or in some cases, its RNA.
The systematic study of the complete DNA sequences (GENOME) of organisms.
A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories for solving biological problems including manipulation of models and datasets.
Sequential operating programs and data which instruct the functioning of a digital computer.
The original member of the family of endothelial cell growth factors referred to as VASCULAR ENDOTHELIAL GROWTH FACTORS. Vascular endothelial growth factor-A was originally isolated from tumor cells and referred to as "tumor angiogenesis factor" and "vascular permeability factor". Although expressed at high levels in certain tumor-derived cells it is produced by a wide variety of cell types. In addition to stimulating vascular growth and vascular permeability it may play a role in stimulating VASODILATION via NITRIC OXIDE-dependent pathways. Alternative splicing of the mRNA for vascular endothelial growth factor A results in several isoforms of the protein being produced.
A cell surface protein-tyrosine kinase receptor that is overexpressed in a variety of ADENOCARCINOMAS. It has extensive homology to and heterodimerizes with the EGF RECEPTOR, the ERBB-3 RECEPTOR, and the ERBB-4 RECEPTOR. Activation of the erbB-2 receptor occurs through heterodimer formation with a ligand-bound erbB receptor family member.
A PDGF receptor that binds specifically to the PDGF-B chain. It contains a protein-tyrosine kinase activity that is involved in SIGNAL TRANSDUCTION.
Specific receptors on cell membranes that react with PLATELET-DERIVED GROWTH FACTOR, its analogs, or antagonists. The alpha PDGF receptor (RECEPTOR, PLATELET-DERIVED GROWTH FACTOR ALPHA) and the beta PDGF receptor (RECEPTOR, PLATELET-DERIVED GROWTH FACTOR BETA) are the two principle types of PDGF receptors. Activation of the protein-tyrosine kinase activity of the receptors occurs by ligand-induced dimerization or heterodimerization of PDGF receptor types.
A cell surface receptor involved in regulation of cell growth and differentiation. It is specific for EPIDERMAL GROWTH FACTOR and EGF-related peptides including TRANSFORMING GROWTH FACTOR ALPHA; AMPHIREGULIN; and HEPARIN-BINDING EGF-LIKE GROWTH FACTOR. The binding of ligand to the receptor causes activation of its intrinsic tyrosine kinase activity and rapid internalization of the receptor-ligand complex into the cell.
A TIE receptor tyrosine kinase that is found almost exclusively on ENDOTHELIAL CELLS. It is required for both normal embryonic vascular development (NEOVASCULARIZATION, PHYSIOLOGIC) and tumor angiogenesis (NEOVASCULARIZATION, PATHOLOGIC).
Hypertension due to RENAL ARTERY OBSTRUCTION or compression.
Narrowing or occlusion of the RENAL ARTERY or arteries. It is due usually to ATHEROSCLEROSIS; FIBROMUSCULAR DYSPLASIA; THROMBOSIS; EMBOLISM, or external pressure. The reduced renal perfusion can lead to renovascular hypertension (HYPERTENSION, RENOVASCULAR).
The circulation of the BLOOD through the MICROVASCULAR NETWORK.
Use of a balloon catheter for dilation of an occluded artery. It is used in treatment of arterial occlusive diseases, including renal artery stenosis and arterial occlusions in the leg. For the specific technique of BALLOON DILATION in coronary arteries, ANGIOPLASTY, BALLOON, CORONARY is available.
The circulation of blood through the CORONARY VESSELS of the HEART.
A branch of the abdominal aorta which supplies the kidneys, adrenal glands and ureters.
The finer blood vessels of the vasculature that are generally less than 100 microns in internal diameter.

Regulation of the hypoxia-inducible transcription factor 1alpha by the ubiquitin-proteasome pathway. (1/3793)

HIF-1alpha (hypoxia-inducible factor 1alpha) is a basic-helix-loop-helix PAS (Per/Arnt/Sim) transcription factor that, under hypoxic conditions, dimerizes with a partner factor, the basic-helix-loop-helix/PAS protein Arnt, to recognize hypoxia-responsive elements of target genes. It has recently been demonstrated that HIF-1alpha protein but not mRNA levels are dramatically up-regulated in response to hypoxia. Here we show that inhibitors of 26 S proteasome activity produced a dramatic accumulation of endogenous as well as transfected HIF-1alpha protein under normoxic conditions, whereas the levels of Arnt protein were not affected. HIF-1alpha was polyubiquitinated in vivo under normoxic conditions, indicating rapid degradation via the ubiquitin-proteasome pathway. This degradation process appeared to target a region within the C terminus of HIF-1alpha. Importantly, HIF-1alpha ubiquitination was drastically decreased under hypoxic conditions. Up-regulation of HIF-1alpha protein by proteasome inhibitors did not result in transcriptional activation of reporter genes, indicating either the requirement of additional regulatory steps to induce functional activity of HIF-1alpha or the inability of polyubiquitinated forms of HIF-1alpha to mediate hypoxic signal transduction. In support of both these notions, we demonstrate that HIF-1alpha showed hypoxia-dependent translocation from the cytoplasm to the nucleus and that this regulatory mechanism was severely impaired in the presence of proteasome inhibitors. Taken together, these data demonstrate that the mechanism of hypoxia-dependent activation of HIF-1alpha is a complex multistep process and that stabilization of HIF-1alpha protein levels is not sufficient to generate a functional form.  (+info)

Impaired physiological responses to chronic hypoxia in mice partially deficient for hypoxia-inducible factor 1alpha. (2/3793)

Chronic hypoxia induces polycythemia, pulmonary hypertension, right ventricular hypertrophy, and weight loss. Hypoxia-inducible factor 1 (HIF-1) activates transcription of genes encoding proteins that mediate adaptive responses to hypoxia, including erythropoietin, vascular endothelial growth factor, and glycolytic enzymes. Expression of the HIF-1alpha subunit increases exponentially as O2 concentration is decreased. Hif1a-/- mouse embryos with complete deficiency of HIF-1alpha due to homozygosity for a null allele at the Hif1a locus die at midgestation, with multiple cardiovascular malformations and mesenchymal cell death. Hif1a+/- heterozygotes develop normally and are indistinguishable from Hif1a+/+ wild-type littermates when maintained under normoxic conditions. In this study, the physiological responses of Hif1a+/- and Hif1a+/+ mice exposed to 10% O2 for one to six weeks were analyzed. Hif1a+/- mice demonstrated significantly delayed development of polycythemia, right ventricular hypertrophy, pulmonary hypertension, and pulmonary vascular remodeling and significantly greater weight loss compared with wild-type littermates. These results indicate that partial HIF-1alpha deficiency has significant effects on multiple systemic responses to chronic hypoxia.  (+info)

Inhibition of hypoxia-inducible factor 1 activation by carbon monoxide and nitric oxide. Implications for oxygen sensing and signaling. (3/3793)

It has been proposed that cells sense hypoxia by a heme protein, which transmits a signal that activates the heterodimeric transcription factor hypoxia-inducible factor 1 (HIF-1), thereby inducing a number of physiologically relevant genes such as erythropoietin (Epo). We have investigated the mechanism by which two heme-binding ligands, carbon monoxide and nitric oxide, affect oxygen sensing and signaling. Two concentrations of CO (10 and 80%) suppressed the activation of HIF-1 and induction of Epo mRNA by hypoxia in a dose-dependent manner. In contrast, CO had no effect on the induction of HIF-1 activity and Epo expression by either cobalt chloride or the iron chelator desferrioxamine. The affinity of CO for the putative sensor was much lower than that of oxygen (Haldane coefficient, approximately 0.5). Parallel experiments were done with 100 microM sodium nitroprusside, a nitric oxide donor. Both NO and CO inhibited HIF-1 DNA binding by abrogating hypoxia-induced accumulation of HIF-1alpha protein. Moreover, both NO and CO specifically targeted the internal oxygen-dependent degradation domain of HIF-1alpha, and also repressed the C-terminal transactivation domain of HIF-1alpha. Thus, NO and CO act proximally, presumably as heme ligands binding to the oxygen sensor, whereas desferrioxamine and perhaps cobalt appear to act at a site downstream.  (+info)

Induction and nuclear translocation of hypoxia-inducible factor-1 (HIF-1): heterodimerization with ARNT is not necessary for nuclear accumulation of HIF-1alpha. (4/3793)

Hypoxia-inducible factor-1 (HIF-1) is a master regulator of mammalian oxygen homeostasis. HIF-1 consists of two subunits, HIF-1alpha and the aryl hydrocarbon receptor nuclear translocator (ARNT). Whereas hypoxia prevents proteasomal degradation of HIF-1alpha, ARNT expression is thought to be oxygen-independent. We and others previously showed that ARNT is indispensable for HIF-1 DNA-binding and transactivation function. Here, we have used ARNT-mutant mouse hepatoma and embryonic stem cells to examine the requirement of ARNT for accumulation and nuclear translocation of HIF-1alpha in hypoxia. As shown by immunofluorescence, HIF-1alpha accumulation in the nucleus of hypoxic cells was independent of the presence of ARNT, suggesting that nuclear translocation is intrinsic to HIF-1alpha. Co-immunoprecipitation of HIF-1alpha together with ARNT could be performed in nuclear extracts but not in cytosolic fractions, implying that formation of the HIF-1 complex occurs in the nucleus. A proteasome inhibitor and a thiol-reducing agent could mimic hypoxia by inducing HIF-1alpha in the nucleus, indicating that escape from proteolytic degradation is sufficient for accumulation and nuclear translocation of HIF-1alpha. During biochemical separation, both HIF-1alpha and ARNT tend to leak from the nuclei in the absence of either subunit, suggesting that heterodimerization is required for stable association within the nuclear compartment. Nuclear stabilization of the heterodimer might also explain the hypoxically increased total cellular ARNT levels observed in some of the cell lines examined.  (+info)

Molecular mechanisms of transcription activation by HLF and HIF1alpha in response to hypoxia: their stabilization and redox signal-induced interaction with CBP/p300. (5/3793)

Hypoxia-inducible factor 1 alpha (HIF1alpha) and its related factor, HLF, activate expression of a group of genes such as erythropoietin in response to low oxygen. Transfection analysis using fusion genes of GAL4DBD with various fragments of the two factors delineated two transcription activation domains which are inducible in response to hypoxia and are localized in the C-terminal half. Their sequences are conserved between HLF and HIF1alpha. One is designated NAD (N-terminal activation domain), while the other is CAD (C-terminal activation domain). Immunoblot analysis revealed that NADs, which were rarely detectable at normoxia, became stabilized and accumulated at hypoxia, whereas CADs were constitutively expressed. In the mammalian two-hybrid system, CAD and NAD baits enhanced the luciferase expression from a reporter gene by co-transfection with CREB-binding protein (CBP) prey, whereas CAD, but not NAD, enhanced beta-galactosidase expression in yeast by CBP co-expression, suggesting that NAD and CAD interact with CBP/p300 by a different mechanism. Co-transfection experiments revealed that expression of Ref-1 and thioredoxin further enhanced the luciferase activity expressed by CAD, but not by NAD. Amino acid replacement in the sequences of CADs revealed a specific cysteine to be essential for their hypoxia-inducible interaction with CBP. Nuclear translocation of thioredoxin from cytoplasm was observed upon reducing O2 concentrations.  (+info)

Repression of dioxin signal transduction in fibroblasts. Identification Of a putative repressor associated with Arnt. (6/3793)

Heterodimeric complexes of basic helix-loop-helix/PAS transcription factors are involved in regulation of diverse physiological phenomena such as circadian rhythms, reaction to low oxygen tension, and detoxification. In fibroblasts, the basic helix-loop-helix/PAS heterodimer consisting of the ligand-inducible dioxin receptor and Arnt shows DNA-binding activity, and the receptor and Arnt are able to activate transcription when fused to a heterologous DNA-binding domain. However, fibroblasts are nonresponsive to dioxin with regard to induction mediated by the DNA response element recognized by the receptor and Arnt. Here we demonstrate that Arnt is associated with a fibroblast-specific factor, forming a complex that is capable of binding the dioxin response element. This factor may function as a repressor since negative regulation of target gene induction appears to be abolished by inhibition of histone deacetylase activity by trichostatin A. Finally, the negative regulatory function of this factor appears to be restricted for dioxin signaling since Arnt was able to mediate, together with hypoxia-inducible factor-1alpha, transcriptional activation in hypoxic cells. Taken together, these data suggest that fibroblast-specific inhibition of dioxin responsiveness involves recruitment by Arnt of a cell type- and signaling pathway-specific corepressor associated with a histone deacetylase.  (+info)

Molecular cloning of cDNAs encoding hypoxia-inducible factor (HIF)-1alpha and -2alpha of bovine arterial endothelial cells. (7/3793)

Hypoxia-inducible factor (HIF)-1alpha and -2alpha are two basic helix-loop-helix/PAS domain transcriptional factors that mediate hypoxia-induced gene expression. We found that bovine arterial endothelial cells (BAEC) expressed both HIF-1alpha and -2alpha by RT-PCR and then isolated cDNAs encoding these two transcriptional factors of BAEC. The deduced amino acid sequences of both HIF-1alpha and -2alpha showed high homologies among mammalian species. Northern blot analysis indicated that the mRNAs for HIF-1alpha and -2alpha from BAEC showed a size of approx. 5.5 and 6.2 kilobases, respectively and that both mRNAs were constitutively expressed and not induced by hypoxia in BAEC.  (+info)

Defective vascularization of HIF-1alpha-null embryos is not associated with VEGF deficiency but with mesenchymal cell death. (8/3793)

Hypoxia-inducible factor 1 (HIF-1) is a dimeric transcription factor composed of HIF-1alpha and HIF-1beta subunits that plays an essential role in mammalian O2 homeostasis. In Hif1a-/- knockout mice, complete deficiency of HIF-1alpha resulted in cardiac and vascular malformations and embryonic lethality at E10.5. Between E8. 75 and E9.25 striking vascular regression and abnormal remodeling occurred in the cephalic region concomitant with marked mesenchymal cell death. Similar vascular defects were observed in HIF-1alpha- and VEGF-deficient embryos and VEGF mRNA expression was not induced by hypoxia in Hif1a-/- embryonic stem cells. Surprisingly, Hif1a-/- embryos demonstrated increased VEGF mRNA expression compared to wild-type embryos. In tissue culture cells, VEGF mRNA expression was induced by glucose deprivation independent of HIF-1alpha, providing a mechanism for increased VEGF mRNA expression in Hif1a-/- embryos, in which absence of adequate tissue perfusion resulted in both O2 and glucose deprivation. Rather than being associated with VEGF deficiency, the vascular defects in Hif1a-/- embryos were spatially correlated with cell death, the onset of which preceded vascular regression.  (+info)

Background: During myocardial ischemia, hypoxia-inducible factors are stabilized and provide protection from ischemia and reperfusion injury. Recent studies show that myocyte-specific hypoxia-inducible factor 2A promotes myocardial ischemia tolerance through induction of epidermal growth factor, amphiregulin. Here, the authors hypothesized that hypoxia-inducible factor 2A may enhance epidermal growth factor receptor 1 (ERBB1) expression in the myocardium that could interface between growth factors and its effect on providing tolerance to ischemia and reperfusion injury. Methods: Human myocardial tissues were obtained from ischemic heart disease patients and normal control patients to compare ERBB1 expression. Myocyte-specific Hif2a or ErbB1 knockout mice were generated to observe the effect of Hif2a knockdown in regulating ERBB1 expression and to examine the role of ERBB1 during myocardial ischemia and reperfusion injury. Results: Initial studies of myocardial tissues from patients with ischemic ...
Definition of hypoxia-inducible factor 1, alpha subunit in the Definitions.net dictionary. Meaning of hypoxia-inducible factor 1, alpha subunit. What does hypoxia-inducible factor 1, alpha subunit mean? Information and translations of hypoxia-inducible factor 1, alpha subunit in the most comprehensive dictionary definitions resource on the web.
The differential expression from the hypoxia-inducible factor-alpha (HIF-) isoforms in your skin of mice influences vascular resistance and it is correlated with homeostatic regulation of nitric oxide synthesis. 34). On the other hand, HIF-2 deletion in keratinocytes (= 10) considerably reduced basal systolic (103 mmHg) and diastolic (82 mmHg) stresses, leading to systemic hypotension. Fig. 3. Murine keratinocyte manifestation of HIF-1/-2 subunits modulates systemic blood circulation pressure. (< 0.01) and diastolic (111 mmHg vs. 89 mmHg, < 0.01) bloodstream stresses were significantly increased in day time 14 in Ang-IICtreated WT mice in comparison with vehicle-treated settings (Fig. S6= 7) there is a significant upsurge in both systolic (187 mm/Hg vs. 170 mm/Hg) and diastolic (138 mmHg vs. 119 mmHg) bloodstream stresses weighed against littermate settings (Fig. 4= 7), where substantial safety against Ang-IICinduced hypertension was noticed, with attenuation in both systolic and diastolic ...
This gene encodes the alpha subunit of transcription factor hypoxia-inducible factor-1 (HIF-1), which is a heterodimer composed of an alpha and a beta subunit. HIF-1 functions as a master regulator of cellular and systemic homeostatic response to hypoxia by activating transcription of many genes, including those involved in energy metabolism, angiogenesis, apoptosis, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia. HIF-1 thus plays an essential role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jul 2011 ...
The vascular endothelial growth factors (VEGF) plays major roles during tumor development. VEGF expression is regulated by the transcription factor HIF (hypoxia inducible factor) which is very sensitive to oxygene variations. We will show here that HIF1alpha is today a good prognostic and diagnostic marker for an increasing number of cancers from various origins. Furthermore, the reduction of the expression or the activity of HIF1alpha impairs tumour angiogenesis and subsequently growth. Altogether, these results suggest that HIF1alpha could be an interesting target in cancer therapy.
accepted 12 December 2013. Abstract. Background: Lymphomas are B and/or T cell clonal neoplasms in various states of differentiation, characteristically compromising lymph nodes. They are constituted by B and T lymphocytes that reach the node by chemokine-mediated recruitment including CXCL13. Hypoxia-inducible transcription factor (HIF-1α) plays a role in cellular adaptation to oxygen concentration changes. It also regulates expression of chemokines such as CXCL12, CCL20, and CCL5 as well as some of their receptors such as CCR7 and CXCR4.. Methods: We performed in silico analysis of the CXCL13 promoter, pharmacologic modulation of HIF-1α activity and, using reporter plasmids, site-directed mutation and DNA-protein interaction analysis we analyzed the relation between HIF-1α activity and CXCL13 expression. Moreover, we did tissue microarray and immunohistochemistry to see the expression of HIF-1α and CXCL13.. Results: This study detected three possible HIF-1α binding sites suggesting that ...
Hypoxia-inducible factor 1alpha stabilization by carbon monoxide results in cytoprotective preconditioning. Proc Natl Acad Sci U S A. 2007 Mar 20; 104(12):5109-14 ...
intestinal epithelial cells (IECs) present in the metabolic state of low oxygen tension is called physiological hypoxia. An important factor in maintaining intestinal homeostasis is a transcription factor hypoxia-inducible factor (HIF), which is stabilized under hypoxic conditions and mediate the homeostatic response to low oxygen tension IEC. To identify the target HIF transcription in IEC, chromatin immunoprecipitation (CHIP) is performed in Caco-2 IECs using HIF-1α […]. ...
Title: Hypoxia Inducible Factor-1 as a Therapeutic Target in Cerebral Ischemia. VOLUME: 4 ISSUE: 3. Author(s):Penelope Aguilera, Edgar Vazquez-Contreras, Carlos Daniel Gomez-Martínez and Maria Elena Chanez Cardenas. Affiliation:Laboratorio de Patologia Vascular Cerebral, Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez. Av Insurgentes Sur 3877, Mexico D.F. 14269, Mexico.. Keywords:Hypoxia inducible factor, ischemic preconditioning, prolyl hydroxylase, cerebral ischemia. Abstract: Cerebral ischemia is the third leading cause of death in industrialized countries and an important health system problem with no efficient treatment to date. The reduction in oxygen and glucose supply triggers a cascade of events such as excitotoxicity, oxidative stress, inflammation, apoptosis, and an adjustment of the gene expression program. The hypoxia inducible factor-1 (HIF-1) is a transcription factor that mediates the adaptive responses to the reduction in oxygen availability. HIF-1 ...
Supplementary MaterialsSupplementary Information srep22784-s1. decreased the expression of HIF-1 target genes and reduced glycolysis in normoxic cancer cells. NECAB3 mutants that binds Mint3 but lacks an intact monooxygenase domain also inhibited HIF-1 activation. Inhibition of NECAB3 in cancer cells by either expressing shRNAs or generating a dominant negative mutant reduced tumourigenicity. Taken together, the data indicate that NECAB3 is a promising new target for cancer therapy. At normal oxygen levels, or normoxia, cells use the mitochondria to generate energy. When oxygen is not available, as under hypoxic conditions, cells shift to cytosolic glycolysis, an oxygen-independent pathway that converts glucose to pyruvate to produce ATP. The shift is accomplished by activating the transcription factor hypoxia-inducible factor-1 (HIF-1). HIF-1 is the master regulator of gene expression during hypoxia, and consists of a regulatory subunit (HIF) and a constitutive subunit. Three forms of HIF have ...
The transcription factor hypoxia-inducible factor 1 (HIF1), which regulates oxygen homeostasis, is activated by stabilisation of the HIF1α subunit under low-oxygen conditions. Several studies have hinted that HIF1 might also have a role in cell adhesion and motility; now, Roser Buscà and colleagues (p. 2992) establish that HIF1 is important in keratinocyte migration during wound healing. The authors previously used an in vitro scratch-wound assay to show that several targets of HIF1 were upregulated in keratinocyte sheets in response to wounding, and they now show that HIF1α protein levels increase under the same conditions. Moreover, they demonstrate that HIF1α stabilisation is regulated by the PI3K-Akt pathway and, unusually, occurs under normoxic conditions. When HIF1α is depleted by siRNA, keratinocyte migration is impaired; additionally, HIF1α depletion abolishes the scratch-wound-dependent upregulation of the ECM protein laminin-332 (which is important in wound healing). The authors ...
Mitochondria have various essential functions in metabolism and in determining cell fate during apoptosis. In addition, mitochondria are also important nodes in a number of signaling pathways. For example, mitochondria can modulate signals transmitted by second messengers such as calcium. Because mitochondria are also major sources of reactive oxygen species (ROS), they can contribute to redox signaling-for example, by the production of ROS such as hydrogen peroxide that can reversibly modify cysteine residues and thus the activity of target proteins. Mitochondrial ROS production is thought to play a role in hypoxia signaling by stabilizing the oxygen-sensitive transcription factor hypoxia-inducible factor-1α. New evidence has extended the mechanism of mitochondrial redox signaling in cellular responses to hypoxia in interesting and unexpected ways. Hypoxia altered the microtubule-dependent transport of mitochondria so that the organelles accumulated in the perinuclear region, where they ...
Asparagine-803 in the C-terminal transactivation domain of human hypoxia-inducible factor (HIF)-1 alpha-subunit is hydroxylated by factor inhibiting HIF-1 (FIH-1) under normoxic conditions causing abrogation of the HIF-1alpha/p300 interaction. NMR and other analyses of a hydroxylated HIF fragment
When oxygen is limiting, cells adjust their metabolism through the transcription factors hypoxia-inducible factors (HIFs). Loss of function of VHL, a protein necessary to maintain the low abundance of HIFs under normoxic conditions, results in constitutively active HIFs and contributes to some forms of cancer, in particular clear cell renal carcinoma (ccRCC). Li et al. found through metabolomic analysis that primary human ccRCCs had higher glucose metabolism but lower gluconeogenesis than matched normal kidney tissue. The tumors universally had reduced or undetectable amounts of the enzyme fructose-1,6-bisphosphatase 1 (FBP1). Knockdown of endogenous FBP1 enhanced the proliferation of HK-2 cells, a proximal tubule cell line. Ectopic expression of FBP1 (to amounts similar to those in HK-2 cells) in a ccRCC line inhibited tumor growth when xenografted in mice and inhibited anchorage-dependent and anchorage-independent growth in culture. Ectopic expression of FBP1 in ccRCC cells reduced glycolysis ...
The HIF signaling pathway is a crucial way in which tumors can circumvent the constraints of regions of low oxygen (hypoxia) to induce angiogenesis and maintain proliferation. The oxygen regulated subunit of the transcription factor hypoxia-inducible factor 1 (HIF1), HIF1αlpha, is a positive factor in tumor growth and its expression has been correlated with poor patient prognosis in a number of settings.. We here present in vitro and in vivo data for a novel series of orally available small-molecule HIF signaling modulators that show nanomolar inhibition of the HIF signaling pathway in addition to potent anti-proliferative activity against a large number of cell lines derived from solid and blood tumors (EC50 in the range 1-100nM). Phenotypically, the compounds elicit an initial G2/M arrest, followed by the induction of caspase-3/7 and the onset of apoptosis.. The in vitro results also translate into in vivo animal models. The lead compounds from the series show efficacy in tumor xenograft ...
TY - JOUR. T1 - Effects of aging and hypoxia-inducible factor-1 activity on angiogenic cell mobilization and recovery of perfusion after limb ischemia. AU - Bosch-Marce, Marta. AU - Okuyama, Hiroaki. AU - Wesley, Jacob B.. AU - Sarkar, Kakali. AU - Kimura, Hideo. AU - Liu, Ye V.. AU - Zhang, Huafeng. AU - Strazza, Marianne. AU - Rey, Sergio. AU - Savino, Lindsey. AU - Zhou, Yi Fu. AU - McDonald, Karin R.. AU - Na, Youn. AU - Vandiver, Scott. AU - Rabi, Alireza. AU - Shaked, Yuval. AU - Kerbel, Robert. AU - LaVallee, Theresa. AU - Semenza, Gregg L.. PY - 2007/12/1. Y1 - 2007/12/1. N2 - Ischemia is a stimulus for production of angiogenic cytokines that activate local vascular cells and mobilize angiogenic cells to the circulation. These responses are impaired in elderly patients with peripheral arterial disease. Hypoxia-inducible factor (HIF)-1 mediates adaptive responses to ischemia, including production of angiogenic cytokines. In this study, we demonstrate that aging and HIF-1 loss-of-function ...
The kidneys are exposed to hypoxic conditions during development. Hypoxia-inducible factor (HIF), an important mediator of the response to hypoxia, is believed to have an important role in development. However, the relationship between HIF and branching morphogenesis has not been elucidated clearly. In this study, we examined whether HIF regulates kidney development. We harvested kidneys from day 13 rat embryos (E13K5) and cultured the organs under normoxic (20% 02/5% CO2) or hypoxic (5% 02/5% CO2) conditions. We evaluated the kidneys based on morphology and gene expression. El3K5 cultured under hypoxic conditions had significantly more ureteric bud (UB) branching than the E13Ks cultured under normoxic conditions. In addition, the mRNA levels of GDNF and GDNF receptor (GFR-alpha l), increased under hypoxic conditions in E13K5. When we cultured E13Ks( with the HIF-1 alpha inhibitor digoxin or with siRNA targeting HIF-l alpha under hypoxic conditions, we did not observe increased UB branching. In ...
The phosphatidylinositol 3-kinase (PI3K) signaling pathway has inherent oncogenic potential. It is up-regulated in diverse human cancers by either a gain of function in PI3K itself or in its downstream target Akt or by a loss of function in the negative regulator PTEN. However, the complete consequences of this up-regulation are not known. Here we show that insulin and epidermal growth factor or an inactivating mutation in the tumor suppressor PTEN specifically increase the protein levels of hypoxia-inducible factor (HIF) 1alpha but not of HIF-1beta in human cancer cell lines. This specific elevation of HIF-1alpha protein expression requires PI3K signaling. In the prostate carcinoma-derived cell lines PC-3 and DU145, insulin- and epidermal growth factor-induced expression of HIF-1alpha was inhibited by the PI3K-specific inhibitors LY294002 and wortmannin in a dose-dependent manner. HIF-1beta expression was not affected by these inhibitors. Introduction of wild-type PTEN into the PTEN-negative ...
The hypoxia-mediated response of tumours is a major determining factor in growth and metastasis. Understanding tumour biology under hypoxic conditions is crucial for the development of antiangiogenic therapy. Using one of the largest cohorts of rectal adenocarcinomas to date, this study investigated hypoxia-inducible factor-1 alpha (HIF-1 alpha) and HIF-2 alpha protein expression in relation to rectal cancer recurrence and cancer-specific survival. Patients (n = 90) who had undergone surgery for rectal adenocarcinoma, with no prior neoadjuvant therapy or metastatic disease, and for whom adequate follow-up data were available were selected. Microvessel density (MVD), HIF-1 alpha and HIF-2 alpha expressions were assessed immunohistologically with the CD34 antibody for vessel identification and the NB100-131B and NB100-132D3 antibodies for HIF-1 alpha and HIF-2 alpha, respectively. In a multifactorial analysis, results were correlated with tumour stage, recurrence rate and long-term survival. ...
Synthesis and biological evaluation of meta-carborane-containing phenoxyacetanilides as inhibitors of hypoxia-inducible factor (HIF)-1 transcriptional activitySynthesis and biological evaluation of meta-carborane-containing phenoxyacetanilides as inhibitors of hypoxia-inducible factor (HIF)-1 transcriptional activity ...
A great many aspects of the anatomy and physiology of large animals are constrained by the need to match oxygen supply to cellular metabolism and appear likely to involve the regulation of gene expression by oxygen. Some insight into possible underlying mechanisms has been provided by studies of erythropoietin, a haemopoietic growth factor which stimulates red cell production in response to hypoxia. Studies of hypoxia-inducible cis-acting sequences from the erythropoietin gene have led to the recognition of a widespread transcriptional response to hypoxia based on the activation of a DNA-binding complex termed hypoxia-inducible factor-1 (HIF-1). Perturbation of the transcriptional response by particular transition metal ions, iron chelators and certain redox-active agents have suggested a specific oxygen sensing mechanism, perhaps involving a haem protein in a flavoprotein/cytochrome system. In addition to erythropoietin, HIF-1-responsive genes include examples with functions in cellular energy
A great many aspects of the anatomy and physiology of large animals are constrained by the need to match oxygen supply to cellular metabolism and appear likely to involve the regulation of gene expression by oxygen. Some insight into possible underlying mechanisms has been provided by studies of erythropoietin, a haemopoietic growth factor which stimulates red cell production in response to hypoxia. Studies of hypoxia-inducible cis-acting sequences from the erythropoietin gene have led to the recognition of a widespread transcriptional response to hypoxia based on the activation of a DNA-binding complex termed hypoxia-inducible factor-1 (HIF-1). Perturbation of the transcriptional response by particular transition metal ions, iron chelators and certain redox-active agents have suggested a specific oxygen sensing mechanism, perhaps involving a haem protein in a flavoprotein/cytochrome system. In addition to erythropoietin, HIF-1-responsive genes include examples with functions in cellular energy
EGLN1_HUMAN] Cellular oxygen sensor that catalyzes, under normoxic conditions, the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. Hydroxylates a specific proline found in each of the oxygen-dependent degradation (ODD) domains (N-terminal, NODD, and C-terminal, CODD) of HIF1A. Also hydroxylates HIF2A. Has a preference for the CODD site for both HIF1A and HIF1B. Hydroxylated HIFs are then targeted for proteasomal degradation via the von Hippel-Lindau ubiquitination complex. Under hypoxic conditions, the hydroxylation reaction is attenuated allowing HIFs to escape degradation resulting in their translocation to the nucleus, heterodimerization with HIF1B, and increased expression of hypoxy-inducible genes. EGLN1 is the most important isozyme under normoxia and, through regulating the stability of HIF1, involved in various hypoxia-influenced processes such as angiogenesis in retinal and cardiac functionality.[3] [4] [5] [6] [7] ...
A key adaptation to environmental hypoxia is an increase in erythropoiesis, driven by the hormone erythropoietin (EPO) through what is traditionally thought to be primarily a renal response. However, both neurons and astrocytes (the largest subpopulation of glial cells in the CNS) also express EPO following ischemic injury, and this response is known to ameliorate damage to the brain. To investigate the role of glial cells as a component of the systemic response to hypoxia, we created astrocyte-specific deletions of the murine genes encoding the hypoxia-inducible transcription factors HIF-1α and HIF-2α and their negative regulator von Hippel-Lindau (VHL) as well as astrocyte-specific deletion of the HIF target gene Vegf. We found that loss of the hypoxic response in astrocytes does not cause anemia in mice but is necessary for approximately 50% of the acute erythropoietic response to hypoxic stress. In accord with this, erythroid progenitor cells and reticulocytes were substantially reduced in ...
Gene therapy techniques were used to insert a peptide into cultures of human cancer cells that blocked their ability to use the enzyme Hypoxia-inducible factor-1, a heterodimeric transcription factor that enables cell survival under low oxygen conditions by altering the transcription of over 300 genes. Hypoxia inducible factor-1 (HIF-1) is a heterodimeric transcription factor that acts as the master regulator of cellular response to reduced oxygen levels, thus playing a key role in the adaptation, survival, and progression of tumors. There is significant evidence that inhibition of HIF-1 would be beneficial for cancer therapy, since tumor cells must thrive in a microenvironment characterized by lack of oxygen. In previous work, investigators at the University of Southampton (United Kingdom) discovered a cyclic hexapeptide (cyclo-CLLFVY) that inhibited the HIF-1alpha/HIF-1beta protein-protein interaction in vitro and prevented HIF-1-mediated hypoxia-response signaling in cells. This cyclic peptide was
Hypoxia-inducible factor 1 (HIF-1) is found in mammalian cells cultured under reduced O2 tension and is necessary for transcriptional activation mediated by the erythropoietin gene enhancer in hypoxic cells. We show that both HIF-1 subunits are basic-helix-loop-helix proteins containing a PAS domain, defined by its presence in the Drosophila Per and Sim proteins and in the mammalian ARNT and AHR proteins. HIF-1 alpha is most closely related to Sim. HIF-1 beta is a series of ARNT gene products, which can thus heterodimerize with either HIF-1 alpha or AHR. HIF-1 alpha and HIF-1 beta (ARNT) RNA and protein levels were induced in cells exposed to 1% O2 and decayed rapidly upon return of the cells to 20% O2, consistent with the role of HIF-1 as a mediator of transcriptional responses to hypoxia.. ...
TY - JOUR. T1 - Up-regulation of gene expression by hypoxia is mediated predominantly by hypoxia-inducible factor 1 (HIF-1). AU - Greijer, A.E.. AU - Groep, van der, P.. AU - Kemming, D.. AU - Shvarts, A.. AU - Semenza, G.L.. AU - Meijer, G.A.. AU - Wiel, van de, M.A.. AU - Belien, J.A.M.. AU - Diest, van, P.J.. AU - Wall, van der, E.. PY - 2005. Y1 - 2005. U2 - 10.1002/path.1778. DO - 10.1002/path.1778. M3 - Article. C2 - 15906272. VL - 206. SP - 291. EP - 304. JO - Journal of Pathology. JF - Journal of Pathology. SN - 0022-3417. IS - 3. ER - ...
FSH stimulation of granulosa cells (GCs) results in increased hypoxia-inducible factor (HIF)-1alpha protein levels and HIF-1 activity that is necessary for up-regulation of certain FSH target genes including vascular endothelial growth factor. We report that the role of the phosphatidylinositol (PI)-3-kinase/AKT pathway in increasing HIF-1alpha protein in FSH-stimulated GCs extends beyond an increase in mammalian target of rapamycin-stimulated translation. FSH increases phosphorylation of the AKT target mouse double-minute 2 (MDM2); a phosphomimetic mutation of MDM2 is sufficient to induce HIF-1 activity. The PI3-kinase/AKT target forkhead box-containing protein O subfamily 1 (FOXO1) also effects the accumulation of HIF-1alpha as evidenced by the ability of a constitutively active FOXO1 mutant to inhibit the induction by FSH of HIF-1alpha protein and HIF-1 activity. Activation of the PI3-kinase/AKT pathway in GCs by IGF-I is sufficient to induce HIF-1alpha protein but surprisingly not HIF-1 activity.
Poorly oxygenated ( hypoxic) tumors are frequently more aggressive compared to corresponding tumors that are better oxygenated. Adaptation to hypoxia is primarily mediated by two closely related hypoxia inducible transcription factor complexes, HIF-1 and HIF-2, which become stabilized and activated at low oxygen levels. Whether HIF-1 and HIF-2 have different roles in tumorigenesis is an open question and an issue we discuss. With focus on HIF-2, we summarize reported phenotypical changes of HIF genetic models and HIF expression patterns during normal development, in adult non - malignant tissues and in tumors. We further address the much - discussed subject of target gene preferences between HIF-1 and HIF-2, given that both transcription factors bind to the same DNA motif. Finally, we also discuss the observations that the oxygen - sensitive HIF-2 alpha subunit is accumulated and active under non - hypoxic conditions as exemplified by HIF-2 alpha expressing tumor macrophages and neuroblastoma ...
Hypoxia-inducible factor-1alpha is a critical mediator of hypoxia induced apoptosis in cardiac H9c2 and kidney epithelial HK-2 cells. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
References for Abcams Recombinant Human HIF-1 alpha protein (ab48734). Please let us know if you have used this product in your publication
Tumour progression is characterized by massive cellular proliferation associated with alterations of the tumour microenvironment. Hence, the tumour microenvironment is considered to be of great...
Clinical studies using oxygen-sensitive electrodes provided evidence that human tumors contain regions of low pO2. Tumor hypoxia correlates with poor prognosis after treatment (3 , 51) . Recent efforts concentrated on this unique feature of solid tumors to develop antitumor strategies, including the production of drugs that are toxic under hypoxic conditions or the generation of hypoxia-inducible vectors containing concatamerized HRE sites. These vectors activate toxin production under hypoxic conditions (for review, see Ref. 6 ). However, the role of HIF-1α in tumorigenesis is still controversial. Our study provides new information concerning the implication of HIF-1α in tumor growth, vasculogenesis, apoptosis, and differentiation. We generated teratocarcinomas in nude mice by injecting HIF-1α+/+ and HIF-1α−/− ES cells. In agreement with previous publications on HIF-1α-deficient ES cells (52) and on transformed mouse embryonic fibroblasts (52) , our results show that HIF-1α+/+ tumors ...
In the present era of ever-increasing antibiotic resistance and increasingly complex and immunosuppressed patient populations, physicians and
HIF-3 alpha (hypoxia-inducible factor 3-alpha/ HIF3A) represents an isoform of HIF-alpha subunits which heterodimerize with stable beta subunit (HIF-beta) for the regulation of HIF target genes through binding to hypoxia response elements/HRE in the promoter regions.
The hypoxia inducible factor-1 (HIF-1), a heterodimer composed of HIF-1alpha and HIF-1beta, is activated in response to low oxygen tension and serves as the master regulator for cells to adapt to hypoxia. HIF-1 is usually considered to be regulated via degradation of its a-subunit. Recent findings, however, point to the existence of alternative mechanisms of HIF-1 regulation which appear to be important for down-regulating HIF-1 under prolonged and severe oxygen depletion. The aims of my Ph.D. thesis, therefore, were to further elucidate mechanisms involved in such down-regulation of HIF-1. The first part of the thesis addresses the impact of the severity and duration of oxygen depletion on HIF-1alpha protein accumulation and HIF-1 transcriptional activity. A special focus was put on the influence of the transcription factor p53 on HIF-1. I found that p53 only accumulates under prolonged anoxia (but not hypoxia), thus limiting its influence on HIF-1 to severe hypoxic conditions. At low ...
The hypoxia inducible factor-1 (HIF-1), a heterodimer composed of HIF-1alpha and HIF-1beta, is activated in response to low oxygen tension and serves as the master regulator for cells to adapt to hypoxia. HIF-1 is usually considered to be regulated via degradation of its a-subunit. Recent findings, however, point to the existence of alternative mechanisms of HIF-1 regulation which appear to be important for down-regulating HIF-1 under prolonged and severe oxygen depletion. The aims of my Ph.D. thesis, therefore, were to further elucidate mechanisms involved in such down-regulation of HIF-1. The first part of the thesis addresses the impact of the severity and duration of oxygen depletion on HIF-1alpha protein accumulation and HIF-1 transcriptional activity. A special focus was put on the influence of the transcription factor p53 on HIF-1. I found that p53 only accumulates under prolonged anoxia (but not hypoxia), thus limiting its influence on HIF-1 to severe hypoxic conditions. At low ...
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Hypoxia-inducible factor (HIF) regulates the major transcriptional cascade central to the response of all mammalian cells to alterations in oxygen tension. Expression arrays indicate that many hundreds of genes are regulated by this pathway, controlling diverse processes that in turn orchestrate both oxygen delivery and utilization. However, the extent to which HIF exerts direct versus indirect control over gene expression together with the factors dictating the range of HIF-regulated genes remains unclear. Using chromatin immunoprecipitation linked to high throughput sequencing, we identify HIF-binding sites across the genome, independently of gene architecture. Using gene set enrichment analysis, we demonstrate robust associations with the regulation of gene expression by HIF, indicating that these sites operate over long genomic intervals. Analysis of HIF-binding motifs demonstrates sequence preferences outside of the core RCGTG-binding motif but does not reveal any additional absolute sequence
This study explored the possibility that upregulation of Hypoxia Inducible Factor-1 (Hif-1)-responsive genes in Human Umbilical Vein Endothelial Cells (HUVEC) would promote and stabilize HUVEC formation into inchoate vascular beds within artificial collagen gels. This experiment was designed to explore the above possibility by sub-cloning Hif-1α, the related chimeric construct Hif-1α/VP16, and the marker gene dsRed into retroviral expression vectors, producing retroviral vectors containing these genes, and stably transducing HUVEC using these retroviruses. Transduced HUVEC were to be observed in cell culture as well as after implantation into artificial collagen gels that have previously supported vascular bed formation by HUVEC. Our results show, preliminarily, that HUVEC transduced with Hif-1α/VP16 go into cell-cycle arrest. Attempts to transduce HUVEC with Hif-1α failed to achieve high enough transduction efficiency to determine the cells angiogenic potential. This study concluded that more
Hypoxia inducible factor-1 (HIF-1) is a key regulator in hypoxia. It has been suggested to be a critical regulator of neurological outcomes following ischemic s...
Inflammation is a primary response to injury and or infection, allowing the body to eliminate pathogens and/or damaged tissue and to initiate repair processes. Low oxygen levels, or hypoxia, is a key feature of inflamed tissue and is due to damage to the local vasculature and increased oxygen consumption by pathogens and infiltrating immune cells. In addition to being a feature of inflammation, hypoxia also induces and regulates the inflammatory response by inducing the release of inflammatory cytokines, directing immune cell infiltration, and tuning the responses of the immune cells themselves. These effects are largely mediated by a family of hypoxia-inducible transcription factors (HIFs), which serve as the master regulators of cellular responses to inadequate oxygenation and HIFs and their regulatory factors are now emerging as therapeutic targets in a number of disease states. Reviews in this series discuss the roles of hypoxia and HIFs in the regulation of inflammatory pathways, immune ...
Inflammation is a primary response to injury and or infection, allowing the body to eliminate pathogens and/or damaged tissue and to initiate repair processes. Low oxygen levels, or hypoxia, is a key feature of inflamed tissue and is due to damage to the local vasculature and increased oxygen consumption by pathogens and infiltrating immune cells. In addition to being a feature of inflammation, hypoxia also induces and regulates the inflammatory response by inducing the release of inflammatory cytokines, directing immune cell infiltration, and tuning the responses of the immune cells themselves. These effects are largely mediated by a family of hypoxia-inducible transcription factors (HIFs), which serve as the master regulators of cellular responses to inadequate oxygenation and HIFs and their regulatory factors are now emerging as therapeutic targets in a number of disease states. Reviews in this series discuss the roles of hypoxia and HIFs in the regulation of inflammatory pathways, immune ...
Inflammation is a primary response to injury and or infection, allowing the body to eliminate pathogens and/or damaged tissue and to initiate repair processes. Low oxygen levels, or hypoxia, is a key feature of inflamed tissue and is due to damage to the local vasculature and increased oxygen consumption by pathogens and infiltrating immune cells. In addition to being a feature of inflammation, hypoxia also induces and regulates the inflammatory response by inducing the release of inflammatory cytokines, directing immune cell infiltration, and tuning the responses of the immune cells themselves. These effects are largely mediated by a family of hypoxia-inducible transcription factors (HIFs), which serve as the master regulators of cellular responses to inadequate oxygenation and HIFs and their regulatory factors are now emerging as therapeutic targets in a number of disease states. Reviews in this series discuss the roles of hypoxia and HIFs in the regulation of inflammatory pathways, immune ...
Inflammation is a primary response to injury and or infection, allowing the body to eliminate pathogens and/or damaged tissue and to initiate repair processes. Low oxygen levels, or hypoxia, is a key feature of inflamed tissue and is due to damage to the local vasculature and increased oxygen consumption by pathogens and infiltrating immune cells. In addition to being a feature of inflammation, hypoxia also induces and regulates the inflammatory response by inducing the release of inflammatory cytokines, directing immune cell infiltration, and tuning the responses of the immune cells themselves. These effects are largely mediated by a family of hypoxia-inducible transcription factors (HIFs), which serve as the master regulators of cellular responses to inadequate oxygenation and HIFs and their regulatory factors are now emerging as therapeutic targets in a number of disease states. Reviews in this series discuss the roles of hypoxia and HIFs in the regulation of inflammatory pathways, immune ...
Inflammation is a primary response to injury and or infection, allowing the body to eliminate pathogens and/or damaged tissue and to initiate repair processes. Low oxygen levels, or hypoxia, is a key feature of inflamed tissue and is due to damage to the local vasculature and increased oxygen consumption by pathogens and infiltrating immune cells. In addition to being a feature of inflammation, hypoxia also induces and regulates the inflammatory response by inducing the release of inflammatory cytokines, directing immune cell infiltration, and tuning the responses of the immune cells themselves. These effects are largely mediated by a family of hypoxia-inducible transcription factors (HIFs), which serve as the master regulators of cellular responses to inadequate oxygenation and HIFs and their regulatory factors are now emerging as therapeutic targets in a number of disease states. Reviews in this series discuss the roles of hypoxia and HIFs in the regulation of inflammatory pathways, immune ...
Inflammation is a primary response to injury and or infection, allowing the body to eliminate pathogens and/or damaged tissue and to initiate repair processes. Low oxygen levels, or hypoxia, is a key feature of inflamed tissue and is due to damage to the local vasculature and increased oxygen consumption by pathogens and infiltrating immune cells. In addition to being a feature of inflammation, hypoxia also induces and regulates the inflammatory response by inducing the release of inflammatory cytokines, directing immune cell infiltration, and tuning the responses of the immune cells themselves. These effects are largely mediated by a family of hypoxia-inducible transcription factors (HIFs), which serve as the master regulators of cellular responses to inadequate oxygenation and HIFs and their regulatory factors are now emerging as therapeutic targets in a number of disease states. Reviews in this series discuss the roles of hypoxia and HIFs in the regulation of inflammatory pathways, immune ...
Inflammation is a primary response to injury and or infection, allowing the body to eliminate pathogens and/or damaged tissue and to initiate repair processes. Low oxygen levels, or hypoxia, is a key feature of inflamed tissue and is due to damage to the local vasculature and increased oxygen consumption by pathogens and infiltrating immune cells. In addition to being a feature of inflammation, hypoxia also induces and regulates the inflammatory response by inducing the release of inflammatory cytokines, directing immune cell infiltration, and tuning the responses of the immune cells themselves. These effects are largely mediated by a family of hypoxia-inducible transcription factors (HIFs), which serve as the master regulators of cellular responses to inadequate oxygenation and HIFs and their regulatory factors are now emerging as therapeutic targets in a number of disease states. Reviews in this series discuss the roles of hypoxia and HIFs in the regulation of inflammatory pathways, immune ...
Insight into Hypoxia Tolerance in Cowpea Bruchid: Metabolic Repression and Heat Shock Protein Regulation via Hypoxia-Inducible Factor 1. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
The hypoxic response in humans is mediated by the hypoxia-inducible transcription factor (HIF), for which prolyl hydroxylases (PHDs) act as oxygen-sensing components. The evolutionary origins of the HIF system have been previously unclear. We demonstrate a functional HIF system in the simplest animal, Trichoplax adhaerens: HIF targets in T. adhaerens include glycolytic and metabolic enzymes, suggesting a role for HIF in the adaptation of basal multicellular animals to fluctuating oxygen levels. Characterization of the T. adhaerens PHDs and cross-species complementation assays reveal a conserved oxygen-sensing mechanism. Cross-genomic analyses rationalize the relative importance of HIF system components, and imply that the HIF system is likely to be present in all animals, but is unique to this kingdom.
TY - JOUR. T1 - Inter-connection between mitochondria and HIFs. AU - Tormos, Kathryn V.. AU - Chandel, Navdeep S.. N1 - Copyright: Copyright 2010 Elsevier B.V., All rights reserved.. PY - 2010/4. Y1 - 2010/4. N2 - The transcription factors hypoxia inducible factors 1 and 2 (HIF-1 and HIF-2) regulate multiple responses to physiological hypoxia such as transcription of the hormone erythropoietin to enhance red blood cell proliferation, vascular endothelial growth factor to promote angiogenesis and glycolytic enzymes to increase glycolysis. Recent studies indicate that HIFs also regulate mitochondrial respiration and mitochondrial oxidative stress. Interestingly, mitochondrial metabolism, respiration and oxidative stress also regulate activation of HIFs. In this review, we examine the evidence that mitochondria and HIFs are intimately connected to regulate each other resulting in appropriate responses to hypoxia.. AB - The transcription factors hypoxia inducible factors 1 and 2 (HIF-1 and HIF-2) ...
Fingerprint Dive into the research topics of Rnd3/RhoE Modulates Hypoxia-Inducible Factor 1α/Vascular Endothelial Growth Factor Signaling by Stabilizing Hypoxia-Inducible Factor 1α and Regulates Responsive Cardiac Angiogenesis. Together they form a unique fingerprint. ...
HO-1 (haem oxygenase-1) catalyses the degradation of haem and possesses anti-inflammatory and cytoprotective properties. The role of inflammatory mediators in the pathogenesis of OA (osteoarthritis) is becoming increasingly appreciated. In the present study, we investigated the effects of HO-1 induction in OA and healthy HACs (human articular chondrocytes) in response to inflammatory cytokine IL-1 β (interleukin-1β) under hypoxic conditions. Hypoxia was investigated as it is a more physiological condition of the avascular cartilage. Hypoxic signalling is mediated by HIFs (hypoxia-inducible factors), of which there are two main isoforms, HIF-1α and HIF-2α. Normal and OA chondrocytes were stimulated with IL-1β. This cytokine suppresses HO-1 expression and exerts both catabolic and anti-anabolic effects, while increasing HIF-1α and suppressing HIF-2α protein levels in OA chondrocytes in hypoxia. Induction of HO-1 by CoPP (cobalt protoporphyrin IX) reversed these IL-1β actions. The ...
Hypoxia-inducible factor (HIF) plays an important role in determining patterns of gene expression in cancer. HIF is down-regulated in oxygenated cells by a series of Fe (II) and 2-oxoglutarate dependent dioxygenases that hydroxylate specific residues in the regulatory HIF-alpha subunits. Because these enzymes require ascorbate for activity in vitro we analyzed the effects of ascorbate on HIF in human cancer cell lines. Ascorbate at physiological concentrations (25 micro M) strikingly suppressed HIF-1alpha protein levels and HIF transcriptional targets, particularly when the system was oncogenically activated in normoxic cells. Similar results were obtained with iron supplementation. These results indicate that both ascorbate and iron availability have major effects on HIF, and imply that the system is commonly regulated by limiting hydroxylase activity under normoxic tissue culture conditions.
Ye et al54 found that, in endothelial cells, a gain-of-function mutation of Frizzled-4, increases the level of the transcription factor Sox 17. Through in vitro assays, these authors observed that Sox 17 is required for Norrin/Frizzled-4/Lrp-mediated angiogenesis in a 3D matrix gel. Sox17 may bind β-catenin and influence its transcriptional activity,71,72 but how and at which level these 2 transcription factors act on angiogenesis in vivo is still unknown.. TCF4/β-catenin complex increases von Hippel-Lindau tumor suppressor,73 which is required for inactivation of the transcription factor hypoxia-inducible factor (HIF)1α, which, in turn, is a potent inducer of vascular endothelial growth factor (VEGF). In addition, HIF1 α competes with TCF4 for direct binding to β-catenin.74 β-Catenin/HIF1α interaction occurs at the promoter regions of HIF1α target genes and increases their expression. Taken together, these data suggest that at low levels of oxygen, the interaction of β-catenin with ...
Ye et al54 found that, in endothelial cells, a gain-of-function mutation of Frizzled-4, increases the level of the transcription factor Sox 17. Through in vitro assays, these authors observed that Sox 17 is required for Norrin/Frizzled-4/Lrp-mediated angiogenesis in a 3D matrix gel. Sox17 may bind β-catenin and influence its transcriptional activity,71,72 but how and at which level these 2 transcription factors act on angiogenesis in vivo is still unknown.. TCF4/β-catenin complex increases von Hippel-Lindau tumor suppressor,73 which is required for inactivation of the transcription factor hypoxia-inducible factor (HIF)1α, which, in turn, is a potent inducer of vascular endothelial growth factor (VEGF). In addition, HIF1 α competes with TCF4 for direct binding to β-catenin.74 β-Catenin/HIF1α interaction occurs at the promoter regions of HIF1α target genes and increases their expression. Taken together, these data suggest that at low levels of oxygen, the interaction of β-catenin with ...
Defective function of the von Hippel-Lindau (VHL) tumor suppressor ablates proteolytic regulation of hypoxia-inducible factor alpha subunits (HIF-1alpha and HIF-2alpha), leading to constitutive activation of hypoxia pathways in renal cell carcinoma (RCC). Here we report a comparative analysis of the functions of HIF-1alpha and HIF-2alpha in RCC and non-RCC cells. We demonstrate common patterns of HIF-alpha isoform transcriptional selectivity in VHL-defective RCC that show consistent and striking differences from patterns in other cell types. We also show that HIF-alpha isoforms display unexpected suppressive interactions in RCC cells, with enhanced expression of HIF-2alpha suppressing HIF-1alpha and vice-versa. In VHL-defective RCC cells, we demonstrate that the protumorigenic genes encoding cyclin D1, transforming growth factor alpha, and vascular endothelial growth factor respond specifically to HIF-2alpha and that the proapoptotic gene encoding BNip3 responds positively to HIF-1alpha and negatively
TY - JOUR. T1 - Hypoxia inducible factor-1α inactivation unveils a link between tumor cell metabolism and hypoxia-induced cell death. AU - Favaro, Elena. AU - Nardo, Giorgia. AU - Persano, Luca. AU - Masiero, Massimo. AU - Moserle, Lidia. AU - Zamarchi, Rita. AU - Rossi, Elisabetta. AU - Esposito, Giovanni. AU - Plebani, Mario. AU - Sattler, Ulrike. AU - Mann, Thomas. AU - Mueller-Klieser, Wolfgang. AU - Ciminale, Vincenzo. AU - Amadori, Alberto. AU - Indraccolo, Stefano. PY - 2008/10. Y1 - 2008/10. N2 - Hypoxia and the acquisition of a glycolytic phenotype are intrinsic features of the tumor microenvironment. The hypoxia inducible factor-1α (HIF-1α) pathway is activated under hypoxic conditions and orchestrates a complex transcriptional program that enhances cell survival. Although the consequences of HIF-1α inactivation in cancer cells have been widely investigated, only a few studies have addressed the role of HIF-1α in the survival of cancer cells endowed with different glycolytic ...
The transcription factor hypoxia inducible factor (HIF) -1 drives tumor growth and metastasis and is associated with poor prognosis in breast cancer. Ascorbate can moderate HIF-1 activity in vitro and is associated with HIF pathway activation in a number of cancer types, but whether tissue ascorbate levels influence the HIF pathway in breast cancer is unknown. In this study we investigated the association between tumor ascorbate levels and HIF-1 activation and patient survival in human breast cancer. In a retrospective analysis of human breast cancer tissue, we analysed primary tumor and adjacent uninvolved tissue from 52 women with invasive ductal carcinoma. We measured HIF-1α, HIF-1 gene targets CAIX, BNIP-3 and VEGF, and ascorbate content. Patient clinical outcomes were evaluated against these parameters. HIF-1 pathway proteins were upregulated in tumor tissue and increased HIF-1 activation was associated with higher tumor grade and stage, with increased vascular invasion and necrosis, and with
The hypoxia-inducible transcription factor (HIF) co-ordinates the response of tumours to low oxygen by stimulating genes involved in metabolism and angiogenesis. HIF pathway activation is associated with decreased progression-free survival and increased mortality; compounds that target this pathway are potential agents for the treatment of a range of solid tumour malignancies. Renal cancers are likely to be particularly sensitive to inhibition of the HIF pathway since ~80% show constitutive activation of HIF. We have previously described the di-substituted naphthalene derivative, CL67, which binds to a G-quadruplex higher-order structure in the HIF promoter sequence in vitro. We show here that CL67 blocks HIF expression leading to inhibition of HIF-transactivation and down-regulation of downstream target genes and proteins in renal carcinoma cell lines and in a mouse xenograft model of renal cancer. This inhibition is independent of pathways that control HIF abundance through oxygen-dependant ...
TY - JOUR. T1 - Effects of aging and hypoxia-inducible factor-1 activity on angiogenic cell mobilization and recovery of perfusion after limb ischemia. AU - Bosch-Marce, Marta. AU - Okuyama, Hiroaki. AU - Wesley, Jacob B.. AU - Sarkar, Kakali. AU - Kimura, Hideo. AU - Liu, Ye V.. AU - Zhang, Huafeng. AU - Strazza, Marianne. AU - Rey, Sergio. AU - Savino, Lindsey. AU - Zhou, Yi Fu. AU - McDonald, Karin R.. AU - Na, Youn. AU - Vandiver, Scott. AU - Rabi, Alireza. AU - Shaked, Yuval. AU - Kerbel, Robert. AU - LaVallee, Theresa. AU - Semenza, Gregg L.. N1 - Copyright: Copyright 2008 Elsevier B.V., All rights reserved.. PY - 2007/12. Y1 - 2007/12. N2 - Ischemia is a stimulus for production of angiogenic cytokines that activate local vascular cells and mobilize angiogenic cells to the circulation. These responses are impaired in elderly patients with peripheral arterial disease. Hypoxia-inducible factor (HIF)-1 mediates adaptive responses to ischemia, including production of angiogenic cytokines. In ...
Hypoxia inducible factors (HIF1 and HIF2) have emerged as central regulators of the activity of myeloid cells at inflammatory sites where O|sup|2|/sup| is frequ...
Erythropoiesis must be tightly balanced in order to guarantee adequate oxygen delivery to all tissues in the body. This process relies predominantly on the hormone erythropoietin (EPO) and its transcription factor hypoxia inducible factor (HIF). Accumulating evidence suggests that oxygen-sensitive prolyl hydroxylases (PHDs) are important regulators of this entire system. Here, we describe a novel mouse line with conditional PHD2 inactivation (cKO P2) in renal EPO producing cells, neurons and astrocytes that displayed excessive erythrocytosis due to severe over-production of EPO, exclusively driven by HIF-2α. In contrast, HIF-1α served as a protective factor, ensuring survival of cKO P2 mice with hematocrit values up to 86%. Using different genetic approaches, we show that simultaneous inactivation of PHD2 and HIF-1α resulted in a drastic PHD3 reduction with consequent overexpression of HIF-2α-related genes, neurodegeneration and lethality. Taken together, our results demonstrate for the ...
We demonstrated that tumors from ccRCC patients with VHL biallelic inactivation (ie, loss of function) display a significant increase in PD-L1 expression compared with ccRCC tumors carrying one VHL wild-type allele. Using the inducible VHL 786-O-derived cell lines with varying hypoxia-inducible factor-2 alpha (HIF-2α) stabilization levels, we showed that PD-L1 expression levels positively correlate with VHL mutation and HIF-2α expression. Targeting HIF-2α decreased PD-L1, while HIF-2α overexpression increased PD-L1 mRNA and protein levels in ccRCC cells. Interestingly, chromatin immunoprecipitation and luciferase assays revealed a direct binding of HIF-2α to a transcriptionally active hypoxia-response element in the human PD-L1 proximal promoter in 786-O cells.. ...
COPD is a seriously disabling respiratory condition that inexorably progresses to disability and mortality. It affects approximately 10% of the population globally with a greater prevalence at advanced ages. Airway bacterial infections complicate the disease course in most COPD patients, leading to increased symptoms, more rapid decline in lung function, acute exacerbations and reduced quality of life. With increasing bacterial resistance to antibiotics and adverse effects of conventional treatments, new effective non-antibiotic antimicrobial therapies are urgently needed to manage COPD. Hypoxia-inducible factor (HIF)-1α is an important transcriptional regulator of cellular responses to hypoxia, oxidants and inflammation, and is overexpressed in the lungs of COPD patients. Recent evidence shows that increased HIF-1α expression can upregulate the platelet-activating factor receptor (PAFR) on the airway epithelial surface that is increased in smokers and particularly COPD patients. The receptor ...
Background: Intratumorous hypoxia triggers a broad cellular response mediated by the transcription factor hypoxia inducible factor 1 (HIF-1). HIF-1a concentrations increase during breast carcinogenesis, and are associated with poor prognosis. An earlier study noted two HIF-1a overexpression patterns: diffuse scattered throughout the tissue and confined to perinecrotic cells. Aims: To investigate ... read more the prognostic impact of these different HIF-1a overexpression patterns in relation to its downstream effectors carbonic anhydrase (CA) IX and glucose transporter 1 (GLUT-1). Methods: HIF-1a, CA IX, and GLUT-1 expression was studied by immunohistochemistry, including double staining for CA IX and HIF-1a. Clinical data included disease free survival, lymph node status, and tumour size. Results: HIF-1a overexpression (44% of cases) had a perinecrotic (13.5%) or diffuse staining pattern (30.5%). CA IX expression was detectable in 12.5% of breast cancers, whereas GLUT-1 expression was seen in ...
Atherosclerosis is by far the most frequent underlying cause of coronary artery disease, carotid artery disease and peripheral arterial disease, and is associated with high morbidity and mortality. Hypoxic areas are known to be present in human atherosclerotic lesions, and lesion progression is associated with the formation of lipid-loaded macrophages, increased local inflammation and angiogenesis. The key regulator of hypoxia, hypoxia-inducible factor 1 (HIF-1), plays a key role in the progression of atherosclerosis by initiating and promoting the formation of foam cells, endothelial cell dysfunction, apoptosis, increasing inflammation and angiogenesis. The objective of this review is to summarise the pathological role of HIF-1 in the progression of atherosclerosis. ...
Corrections: Hypoxia-inducible factor 1 alpha-activated angiopoietin-like protein 4 contributes to tumor metastasis via vascular cell adhesion molecule-1/integrin β1 signaling in human hepatocellular ...
Hypoxia inducible factor (HIFs) signaling contributes to malignant cell behavior in glioblastoma (GBM). We investigated a novel HIF2α inhibitor, PT2385, both in vitro, with low-passage patient-derived cell lines, and in vivo, using orthotopic models of glioblastoma. We focused on analysis of HIF2α expression in situ, cell survival/proliferation, and survival in brain tumor-bearing mice treated with PT2385 alone and in combination with standard of care chemoradiotherapy. HIF2α expression increased with glioma grade, with over half of GBM specimens HIF2α positive. Staining clustered in perivascular and perinecrotic tumor regions. Cellular phenotype including proliferation, viability, migration/invasion, and also gene expression were not altered after PT2385 treatment. In the animal model, PT2385 single-agent treatment did improve median overall survival compared to placebo (p = 0.04, n = 21) without a bioluminescence correlate (t = 0.67, p = 0.52). No difference in animal survival was seen in
Solid tumors contain regions of hypoxia, and tumor hypoxia is an important determinant of clinical prognosis (1-3, 34). Although mechanisms by which severe hypoxia renders tumor cells resistant to radiotherapy and chemotherapy have been defined, it is likely that cellular hypoxia has other important consequences. Recent attention has focused on alterations in gene expression and the possibility that these may induce significant changes such as enhanced angiogenic and metastatic behavior (4, 35, 36).. To determine whether the oxygen-regulated transcription factor HIF-1 is activated in solid tumors, we grew tumor xenografts from Hepa-1 cells that were wild type, defective (c4), and revertant (Rc4) for HIF-1β/ARNT. To provide an assay for the activation of HIF-1-dependent gene expression in the tumors, we first analyzed the expression of GLUT3 mRNA. Hepa-1 cells in normoxic culture express this gene at a low level that is strongly induced by hypoxia (21). In hypoxic tissue culture, induction was ...
In this study, we presented that the hypoxic condition corresponding to the oxygen levels in the tissue microenvironment protects peripheral T cells from Ag receptor stimulation-triggered AICD, indicating a possible role of local oxygen concentrations in regulation of immune reactions.. AICD of peripheral T cells is likely to be coregulated by a variety of factors including environmental constituents. These regulatory mechanisms involve costimulatory molecules (7), humoral factors, or chemicals (5), all of which have been shown to involve the Fas/Fas-L system or Bcl-family proteins. Similarly, but mechanistically distinct from AICD, Ag receptor stimulation in naive T cells has been shown to result in apoptosis, in which NF-κB and p73 play a critical role (27). In the present study, we have demonstrated that hypoxia attenuates AICD in peripheral T cells through HIF-1α-mediated expression of AM possibly via an autocrine regulatory loop mechanism. Strikingly, among the hypoxia-inducible and cell ...
Hypoxia activates transcription of genes necessary for adaptation to low oxygen.1,2 The best described response system uses hypoxia-inducible factors (HIFs) composed of the constitutively expressed subunit HIF-1β bound to labile subunits HIF-1α or HIF-2α, forming HIF-1 or HIF-2, respectively.3 HIF expression is regulated by a family of prolyl hydroxylases, PHD1, PHD2, and PHD3, that sense oxygen tension through its binding to an associated iron atom.4,5 When the PHD iron is occupied by O2, these enzymes catalyze a reaction in which one oxygen atom reacts with 2-oxoglutarate to form succinate and CO2 while the other is transferred to a proline residue in a protein substrate, such as HIF-1α, to form a hydroxyproline side chain. Hydroxylation of proline in HIF-1α recruits the von Hippel-Lindau (pVHL) complex, targeting HIF-1α for ubiquitination and proteasomal degradation.6-8 Molecular oxygen is normally rate limiting, and hypoxia causes HIF-1α protein stabilization and accumulation by ...
The pharmacological modulation of putative renoprotective factors hypoxia-inducible factor-1α (HIF-1α) and HIF-1α-regulated vascular endothelial growth factor-A (VEGF-A) in the kidney has therapeutic interest. In human renal proximal tubular HK2 cells, prostaglandin E2 (PGE2) up-regulates HIF-1α and VEGF-A through epidermal growth factor receptor (EGFR)-dependent up-regulation of retinoic acid receptor-β (RARβ). Here we studied the role of mitogen-activated protein kinases (MAPKs) ERK1/2 and p38 and their target kinase, mitogen- and stress activated kinase-1 (MSK1), in the signaling cascade. Treatment of HK2 cells with PGE2 resulted in increased phosphorylation of EGFR, the three studied kinases and the histone H3 (Ser10) at the RARβ gene promoter (the latter has been proposed as a molecular signature of the activated RARβ gene promoter). Prevention of the phosphorylation of EGFR, ERK1/2, p38 MAPK or MSK1 is by incubating, respectively, with AG1478, PD98059, SB203580 or H89 allowed to ...
Hydroxylates HIF-1 alpha at Asp-803 in the C-terminal transactivation domain (CAD). Functions as an oxygen sensor and, under normoxic conditions, the hydroxylation prevents interaction of HIF-1 with transcriptional coactivators including Cbp/p300-interacting transactivator. Involved in transcriptional repression through interaction with HIF1A, VHL and histone deacetylases. Hydroxylates specific Asn residues within ankyrin repeat domains (ARD) of NFKB1, NFKBIA, NOTCH1, ASB4, PPP1R12A and several other ARD-containing proteins. Also hydroxylates Asp and His residues within ARDs of ANK1 and TNKS2, respectively. Negatively regulates NOTCH1 activity, accelerating myogenic differentiation. Positively regulates ASB4 activity, promoting vascular differentiation ...
Hypoxia is a key factor in tumor development, contributing to angiogenesis and radiotherapy resistance. Hypoxia-inducible factor-1 (HIF-1) is a major transcription factor regulating the response of cancer cells to hypoxia. However, tumors also contain areas of more severe oxygen depletion, or anoxia. Mechanisms for survival under anoxia are HIF-1alpha independent in Caenorhabditis elegans and, thus, differ from the hypoxic response. Here we report a differential response of cancer cells to hypoxia and anoxia by demonstrating the induction of activating transcription factor-4 (ATF-4) and growth arrest DNA damage 153 (GADD153) protein specifically in anoxia and the lack of induction in hypoxia. By applying RNAi, ATF-4 induction in anoxia was shown to be independent of HIF-1alpha, and desferrioxamine mesylate (DFO) and cobalt chloride induced HIF-1alpha but not ATF-4 or GADD153. Furthermore, the inductive response of ATF-4 and GADD153 was not related to alterations in or arrest of mitochondrial respiration
Akebia Therapeutics, a biopharmaceutical company focused on developing therapeutics based on hypoxia-inducible factor biology, strengthens its leaders
Many forms of solid tumor have a characteristic feature known as hypoxia, which describes a low or non-existent presence of oxygen in the cellular microenvironment. This decrease in oxygen causes activation of the hypoxia inducible factor (HIF) pathway, which activates the transcription of many genes that cause cell proliferation, metastasis, increased glycolysis and angiogenesis. Increased HIF expression has been linked with poor patient prognosis, increased malignancy, and therapeutic resistance. Previous work in our lab has identified 1 and 2 as inhibitors of the HIF pathway, specifically as disrupters of the p300-HIF-1α complex formation. A library of sulfonamide analogs has been designed and synthesized with the intent of examining the SAR of this series of compounds and improving potency and physicochemical properties as compared with lead compounds 1 and 2. At the end, we have achieved a thorough understanding of the structural features critical for future optimization work ...
Many forms of solid tumor have a characteristic feature known as hypoxia, which describes a low or non-existent presence of oxygen in the cellular microenvironment. This decrease in oxygen causes activation of the hypoxia inducible factor (HIF) pathway, which activates the transcription of many genes that cause cell proliferation, metastasis, increased glycolysis and angiogenesis. Increased HIF expression has been linked with poor patient prognosis, increased malignancy, and therapeutic resistance. Previous work in our lab has identified 1 and 2 as inhibitors of the HIF pathway, specifically as disrupters of the p300-HIF-1α complex formation. A library of sulfonamide analogs has been designed and synthesized with the intent of examining the SAR of this series of compounds and improving potency and physicochemical properties as compared with lead compounds 1 and 2. At the end, we have achieved a thorough understanding of the structural features critical for future optimization work ...
Based on cDNA microarray results, integrin-linked kinase (ILK) emerged as an interesting candidate in hypoxia-mediated survival mechanisms employed by cancer cells. This notion was confirmed here by the following observations: the 5 promoter region of the ilk gene contains hypoxia responsive elements (HRE) that bind hypoxia-inducible factor (HIF) transcription factor complexes and drive HRE-luciferase gene expression in reporter assays; ILK protein and kinase activity are induced following hypoxia; downstream targets of ILK signaling are induced following hypoxia treatment; inhibition of ILK leads to increased apoptosis; and HIF and ILK are co-localized within human cancer tissues. The identification of ILK as a player in hypoxia survival signaling employed by cancer cells further validates ILK as a unique target for cancer therapy ...
Angiogenesis is a linchpin of survival and tissue restoration following ischemia, but also a prerequisite for atherosclerosis. Angiogenesis is induced by a complex interplay of tissue hypoxia, acidosis, and inflammation; conditions coordinated by a myriad of molecular regulators. We have created a switchable transgenic model of microvascular network elaboration allowing day-to-day kinetic analysis. Doxycycline induction of a Tet-regulated constitutively active hypoxia-inducible factor-1a mutant transgene, HIF-1a ^Pro402/564A/Asn803A was targeted to the skin (TetOn-HIF-1a mice). These mice first demonstrate microvascular dilatation on Dox d1, a burst of endothelial proliferation on d3, followed by an exponential decline by d14 -28. Plasma levels of the bone marrow mobilization factors VEGF, PlGF, and SDF1 spike on d3, while tissue levels of these recruitment and retention factors peak at d14. HIF-1 conditioned stroma and activated endothelium recruit large numbers of bone marrow-derived cells of ...
The signal transduction events that modulate the expression of HIF-1α, as well as the subsequent expression of VEGF and other HIF-1-regulated genes, are currently under intensive scrutiny. The results of the present study confirm and extend the earlier report that rapamycin inhibits both the stabilization of HIF-1α and the transcriptional activity of HIF-1 in hypoxic cancer cells (50). Furthermore, we provide genetic evidence to support the conclusion that the rapamycin target protein, mTOR, functions as a positive regulator of HIF-1 activation by hypoxia or the hypoxia-mimetic agent, CoCl2.. A synthesis of the available data indicates that at least two integrated signaling pathways promote the accumulation of HIF-1α in mammalian cells. The first pathway is triggered by hypoxia or CoCl2 and involves the inhibition of a family of PHDs that modify Pro-564 and Pro-402 of HIF-1α (5, 21, 22, 27, 41). The second pathway is triggered by polypeptide growth factors or oncogenic mutations (e.g., PTEN ...
Background: Hypoxia induces adaptive and pathogenic cellular responses, many of which are controlled by microRNA (miRNA). Plasma-based extracellular miRNA have been measured in ischemic and hypoxia-dependent cardiovascular diseases; yet, their regulation and in vivo biological functions remain enigmatic.. Objective: Determine the role of the hypoxia-inducible miR-210 as a circulating messenger controlling hypoxic adaptation in recipient vascular tissue.. Results: MiR-210 is released from hypoxic (4.8 fold-change+ 0.2 SEM) and re-oxygenated (7.5 fold change+0.3) vascular endothelial cells in culture. Plasma levels of miR-210 are elevated in mice chronically exposed to hypoxia (2.1 fold-change+0.4, N=6 mice/group). MiR-210 is also up-regulated in plasma from humans subjected chronically to high altitude (3.7 fold-change+0.7, N=5 Andean women/group at week 36 pregnancy residing at high and low altitudes) and from PAD patients with intermittent claudication (3.5 fold-change+0.7 vs. healthy control, ...
Chris Pugh and David Mole work on the fundamental mechanisms by which organisms adapt to low oxygen tensions (hypoxia)with Peter Ratcliffe FRS, Nuffield Professor of Medicine. The group started studying the control element regulating the erythropoietin gene and discovered that the fundamental mechanisms involved were widespread, controlling a large number of processes including metabolic adaptation, angiogenesis and cell growth. The group has elucidated the underlying oxygen regulatory mechanisms controlling the activity of the transcription factor, hypoxia inducible factor, resulting inpublications in Nature, Science and Cell. The group is continuing to study the biological processes involved with a view to translating this knowledge towards clinical practice in the future. One particular area of interest is renalcancer, where mutations of the von Hippel Lindau gene disable the normal oxygen regulatory mechanism, affecting the phenotype of the cancer. The group receives funding from The ...
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Methods Hypoxia was induced in RASF by incubation with Na2S2O4. TLR3 ligand polyIC, TLR2 ligand peptidoglycan, TLR4 ligand LPS and TLR9 ligand CpG were used to stimulate the cells. Effects of hypoxia on TLR-induced inflammatory mediators were determined by RT-PCR, qPCR and ELISA. Overexpression of HIF-1α as well as knocking-down its expression was used to reveal its fundamental role. RASF-induced inflammatory T cell expansion was determined by flow cytometry analysis of T helper (Th)1/Th17 cells, and IFN-γ/IL-17 production by ELISA after RASF/T cell coculture.. ...
1MZE: Structure of Factor-Inhibiting Hypoxia-Inducible Factor 1: An Asparaginyl Hydroxylase Involved in the Hypoxic Response Pathway
Results: 71 patients were treated, and the MTD was identified at the highest dose level (bevacizumab 15 mg/kg, bortezomib 1.3 mg/m2 ...
Tumor growth, progression and response to the hypoxic tumor microenvironment (TME) involve the action of hypoxia inducible transcription factors, HIF1 and HIF2. HIF is a heterodimeric transcription factor containing an inducible HIFalpha subunit and a constitutively expressed HIFbeta subunit. The signaling pathways operational in macrophages regulating hypoxia induced HIFalpha stabilization remain the subject of intense investigation. Here it was discovered that the PTEN/PI3K/AKT signaling axis controls hypoxia induced HIF1alpha (HIF1A) and HIF2alpha (EPAS1) stability in macrophages. Using genetic mouse models and pan-PI3 kinase as well as isoform specific inhibitors, inhibition of the PI3K/AKT pathway blocked the accumulation of HIFalpha protein and its primary transcriptional target VEGF in response to hypoxia. Moreover, blocking the PI3K/AKT signaling axis promoted the hypoxic degradation of HIFalpha via the 26S proteasome. Mechanistically, a macrophage dominant PI3K isoform (p110gamma) ...
The Centre for Cell Signalling and Molecular Genetics was established in March 2008 by Patrick Maxwell and Margaret Ashcroft. The main goal of the centre is to understand the key cellular mechanisms involved in oxygen sensing and hypoxia signalling in mammalian cells. In particular, the centre has a strong interest in the hypoxia inducible factor (HIF) family of transcription factors and their role in cancer and other diseases. The centre takes multidisciplinary collaborative approaches to pursue scientific questions combining both basic and translational research ...
Study Objective: To evaluate serum values of cluster of differentiation 95 (CD95/FAS), hypoxia-inducible factor 1-alpha (HIF-1 alpha), and tyrosine kinase receptor 2 (Tie-2) as possible biomarkers of disease presence and ...
Dann CE, Bruick RK, Deisenhofer J (2003). "Structure of factor-inhibiting hypoxia-inducible factor 1: An asparaginyl ... alpha subunit inhibitor". CS1 maint: discouraged parameter (link) Lando D, Peet DJ, Whelan DA, Gorman JJ, Whitelaw ML (2002). " ... "Hypoxia-inducible factor (HIF) asparagine hydroxylase is identical to factor inhibiting HIF (FIH) and is related to the cupin ... "Structure of factor-inhibiting hypoxia-inducible factor (HIF) reveals mechanism of oxidative modification of HIF-1 alpha". J. ...
The human HIF1A gene encodes for the alpha subunit, HIF1A of the transcription factor hypoxia-inducible factor (HIF1). Its ... "Activation of hypoxia-inducible transcription factor depends primarily upon redox-sensitive stabilization of its alpha subunit ... is a subunit of a heterodimeric transcription factor hypoxia-inducible factor 1 (HIF-1) that is encoded by the HIF1A gene. The ... alpha subunit (basic helix-loop-helix transcription factor)". Wang GL, Jiang BH, Rue EA, Semenza GL (June 1995). "Hypoxia- ...
Dann C.E. III, Bruick R.K., Deisenhofer J. (2002). Structure of factor-inhibiting hypoxia-inducible factor 1: an asparaginyl ... Webb J.D., Muranyi A., Pugh C.W., Ratcliffe P.J., Coleman M.L. (2009). MYPT1, the targeting subunit of smooth-muscle myosin ... is a substrate for the asparaginyl hydroxylase factor inhibiting hypoxia-inducible factor (FIH).. Biochem. J. 420. с. 327 - 333 ... HIF1AN, FIH1, hypoxia inducible factor 1 alpha subunit inhibitor. Зовнішні ІД. MGI: 2442345 HomoloGene: 9906 GeneCards: HIF1AN ...
Hydroxylation of proline has been shown to be involved in targeting Hypoxia-inducible factor (HIF) alpha subunit (HIF-1 alpha) ... 2001). "Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation". Science. ... Under normoxia (normal oxygen conditions) EGLN1[1] protein hydroxylates the proline at the 564 position of HIF-1 alpha, which ...
... core binding factor alpha 2 subunit MeSH D12.776.930.155.200.300 - core binding factor alpha 3 subunit MeSH D12.776.930.316. ... hypoxia-inducible factor 1, alpha subunit MeSH D12.776.930.125.750.590 - myod protein MeSH D12.776.930.125.750.595 - myogenic ... nf-e2 transcription factor, p45 subunit MeSH D12.776.930.155.200.100 - core binding factor alpha 1 subunit MeSH D12.776.930.155 ... nf-e2 transcription factor, p45 subunit MeSH D12.776.930.323.500.500 - hepatocyte nuclear factor 1-alpha MeSH D12.776.930.323. ...
... hypoxia-inducible factor 1, alpha subunit MeSH D12.776.260.103.750.590 - myod protein MeSH D12.776.260.103.750.595 - myogenic ... nf-e2 transcription factor, p45 subunit MeSH D12.776.260.262.500.500 - hepatocyte nuclear factor 1-alpha MeSH D12.776.260.262. ... hepatocyte nuclear factor 3-alpha MeSH D12.776.260.950.249.750 - hepatocyte nuclear factor 3-beta MeSH D12.776.260.950.249.875 ... nf-e2 transcription factor, p45 subunit MeSH D12.776.260.235.750.750 - maf transcription factors, small MeSH D12.776.260.235. ...
Saydur (2007), "Molecular cloning, characterization and expression of two hypoxia-inducible factor alpha subunits, HIF-1α and ... after approximately one week and is therefore likely under genetic control of hypoxia inducible factor hypoxia inducible factor ... Research in mammals has implicated hypoxia inducible factor (HIF) as a key regulator of gene expression changes in response to ... "Evolution and Regulation of the Downstream Gene of Hypoxia-Inducible Factor-1α in Naked Carp (Gymnocypris przewalskii) from ...
"Entrez Gene: HIF3A hypoxia inducible factor 3, alpha subunit". Drevytska T, Gavenauskas B, Drozdovska S, Nosar V, Dosenko V, ... It is thought that factors containing the alpha-3 subunit are negative regulators of hypoxia-inducible gene expression. At ... hypoxia). The alpha-3 subunit lacks the transactivation domain found in factors containing either the alpha-1 or alpha-2 ... "Molecular characterization and chromosomal localization of a third alpha-class hypoxia inducible factor subunit, HIF3alpha". ...
Hypoxia-inducible factor prolyl hydroxylase 2 (HIF-PH2), or prolyl hydroxylase domain-containing protein 2 (PHD2), is an enzyme ... In normoxia, HIF alpha subunits are marked for the ubiquitin-proteasome degradation pathway through hydroxylation of proline- ... In humans, PHD2 is one of the three isoforms of hypoxia-inducible factor-proline dioxygenase, which is also known as HIF prolyl ... Ozer A, Wu LC, Bruick RK (2005). "The candidate tumor suppressor ING4 represses activation of the hypoxia inducible factor (HIF ...
Mutations in the genes encoding alpha subunits of hypoxia-inducible factors (HIF-alpha) have not previously been identified in ... Hypoxia-inducible factor signaling in pheochromocytoma: turning the rudder in the right direction. J Natl Cancer Inst 2013; 105 ... Ocular Manifestations of Hypoxia-Inducible Factor-2A Paranglioma-Somatostatinoma-Polycythemia Syndrome. J Opthal 2014. DOI: ... neurofibromatosis 1 (NF1), or von Hippel-Lindau (VHL) disease. ...
... enzymatic hydroxylation of a conserved prolyl residue in hypoxia-inducible factor alpha subunits governs capture by the pVHL E3 ... It is a type of hypoxia-inducible factor, a group of transcription factors involved in the physiological response to oxygen ... "Hypoxia inducible factor-alpha binding and ubiquitylation by the von Hippel-Lindau tumor suppressor protein". The Journal of ... "A novel bHLH-PAS factor with close sequence similarity to hypoxia-inducible factor 1alpha regulates the VEGF expression and is ...
E3 Ubiquitin Ligase and the Hypoxia Inducible Factor (HIF) Alpha Subunit with in Vitro Nanomolar Affinities". Journal of ... Hypoxia Inducible Factor 1α Protein-Protein Interface". Chemistry & Biology. 19 (10): 1300-1312. doi:10.1016/j.chembiol.2012.08 ... 8 (1): 830. Bibcode:2017NatCo...8..830M. doi:10.1038/s41467-017-00954-1. PMC 5635026. PMID 29018234. Cardote, Teresa A. F.; ...
Pacak-Zhuang Syndrome Hypoxia-inducible factor 2 alpha (HIF2A) Polycythemia Duodenal somatostatinoma Retinal and choroidal ... Succinate Dehydrogenase Subunit x) MAX (MYC Associated Factor X); TMEM127 (Transmembrane Protein 127) There have been several ... This complication is related to the impact that alpha and beta-adrenoceptor antagonists have on blood vessels combined with the ... Santos JR, Wolf KI, Pacak K (February 2019). "A Necessity, Not a Second Thought: Pre-Operative Alpha-Adrenoceptor Blockade in ...
... does not alter stability of hypoxia-inducible factor (HIF)-1alpha and is not induced by hypoxia or HIF". The Journal of ... N-alpha-acetyltransferase 10 (NAA10) also known as NatA catalytic subunit Naa10 and arrest-defective protein 1 homolog A (ARD1A ... "Effect of connective tissue growth factor on hypoxia-inducible factor 1alpha degradation and tumor angiogenesis". Journal of ... inhibitors repress the transactivation potential of hypoxia-inducible factors independently of direct acetylation of HIF-alpha ...
... family of transcription factors. The alpha and beta subunit are similar in structure and both contain the following domains: N- ... Hypoxia-inducible factors (HIFs) are transcription factors that respond to decreases in available oxygen in the cellular ... Acker T, Plate KH (2004). "Hypoxia and hypoxia inducible factors (HIF) as important regulators of tumor physiology". Cancer ... "Hydroxylation of hypoxia-inducible transcription factors and chemical compounds targeting the HIF-alpha hydroxylases". Current ...
The hypoxia inducible factor (HIF) is a transcriptional complex which is involved in oxygen homeostasis. At normal oxygen ... the alpha subunit of HIF is targeted for degradation by prolyl hydroxylation. This gene encodes an enzyme responsible for this ... 2004). "Regulation of HIF prolyl hydroxylases by hypoxia-inducible factors". J. Cell. Biochem. 92 (3): 491-501. doi:10.1002/jcb ... modulates activity of hypoxia-inducible transcription factors". Biochem. Biophys. Res. Commun. 296 (2): 343-9. doi:10.1016/ ...
... adenosine receptors inhibit LPS-induced hypoxia-inducible factor-1 accumulation in murine astrocytes". Pharmacol Res. 76: 157- ... ATP4A ATPase H+/K+ transporting alpha subunit Chourasia, M.; Sastry, G. M.; Sastry. G. N. (2005). "Proton binding sites and ... The H+/K+ ATPase β subunit stabilizes the H+/K+ ATPase α subunit and is required for function of the enzyme. The β subunit ... The α subunit also has a phosphorylation site (Asp385). The gene ATP4B encodes the β subunit of the H+/K+ ATPase, which is an ~ ...
Lang KJ, Kappel A, Goodall GJ (May 2002). "Hypoxia-inducible factor-1alpha mRNA contains an internal ribosome entry site that ... is a subunit of the HIF-1 transcription factor, which induces transcription of several genes involved in the cellular response ... The hypoxia-inducible factor-1α protein (HIF-1α) ... The HIF-1α internal ribosome entry site (IRES) is an RNA ... The HIF-1α internal ribosome entry site (IRES) allows translation to be maintained under hypoxic cell conditions that inhibit ...
"The length of peptide substrates has a marked effect on hydroxylation by the hypoxia-inducible factor prolyl 4-hydroxylases". J ... The alpha(I) and alpha(II) subunits do not form a mixed alpha(I)alpha(II)beta2 tetramer". J Biol Chem. 272 (28): 17342-8. doi: ... a key enzyme in collagen synthesis composed of two identical alpha subunits and two beta subunits. The encoded protein is one ... "Cloning of the human prolyl 4-hydroxylase alpha subunit isoform alpha(II) and characterization of the type II enzyme tetramer. ...
Hypoxia-inducible factor (HIF) is an evolutionarily conserved transcription factor that allows the cell to respond ... Helaakoski T, Vuori K, Myllylä R, Kivirikko KI, Pihlajaniemi T (June 1989). "Molecular cloning of the alpha-subunit of human ... Smith TG, Robbins PA, Ratcliffe PJ (May 2008). "The human side of hypoxia-inducible factor". British Journal of Haematology. ... Karuppagounder SS, Ratan RR (July 2012). "Hypoxia-inducible factor prolyl hydroxylase inhibition: robust new target or another ...
Proline hydroxylation is also a vital component of hypoxia response via hypoxia inducible factors. In some cases, proline may ... Other hydroxylating agents include flavins, alpha-ketoglutarate-dependent hydroxylases, and some diiron hydroxylases. The ... multi-subunit enzymes prolyl 4-hydroxylase, prolyl 3-hydroxylase and lysyl 5-hydroxylase, respectively. These reactions require ... 17α-Hydroxylase Cholesterol 7 alpha-hydroxylase Dopamine β-hydroxylase Phenylalanine hydroxylase Tyrosine hydroxylase One ...
This core alpha subunit is also involved in regulating the hypoxia-inducible factor-1alpha, a transcription factor important ... Proteasome subunit alpha type-7 also known as 20S proteasome subunit alpha-4 is a protein that in humans is encoded by the ... As a component of alpha ring, proteasome subunit alpha type-7 contributes to the formation of heptameric alpha rings and ... This protein is one of the 17 essential subunits (alpha subunits 1-7, constitutive beta subunits 1-7, and inducible subunits ...
Srp receptor alpha subunit TAF1D: TATA box binding protein associated factor RNA polymerase 1 subunit D TALDO1 encoding protein ... tumor protein 53 inducible protein 11 TRAPPC4: trafficking protein particle complex subunit 4 TRPT1: tRNA 2'-phosphotransferase ... hypoxia upregulated protein 1 IFITM2 encoding protein Interferon induced transmembrane protein 2 IFT46: intraflagellar ... tectorin alpha (nonsyndromic deafness) TH: tyrosine hydroxylase THRSP: thyroid hormone inducible hepatic protein THYN1: ...
Under hypoxic conditions, hypoxia inducible factor one alpha (HIF1A) will stabilize and activate transcription of REDD1, also ... Once the initiation complex is assembled at the 5' cap of mRNA, it will recruit the 40S small ribosomal subunit that is now ... Cytokines like tumor necrosis factor alpha (TNF-alpha) can induce mTOR activity through IKK beta, also known as IKK2. IKK beta ... Upon growth factor binding to the adjacent receptor tyrosine kinase, the adaptor protein GRB2 binds with its SH2 domains. This ...
Walker JE, Saraste M, Runswick MJ, Gay NJ (1982). "Distantly related sequences in the alpha- and beta-subunits of ATP synthase ... "The stimulation of glycolysis by hypoxia in activated monocytes is mediated by AMP-activated protein kinase and inducible 6- ... studies have confirmed that modification from multiple transcription factors in the 5' flanking region regulates the amount of ... I-Type: Inducible This isoform's name is a result of its increased expression in response to hypoxic stress; its formation is ...
"Regulation of tumor angiogenesis by p53-induced degradation of hypoxia-inducible factor 1alpha". Genes & Development. 14 (1): ... Bálint E, Bates S, Vousden KH (July 1999). "Mdm2 binds p73 alpha without targeting degradation". Oncogene. 18 (27): 3923-9. doi ... "ATM-mediated serine 72 phosphorylation stabilizes ribonucleotide reductase small subunit p53R2 protein against MDM2 to DNA ... In addition, MDM2 has p53-independent transcription factor-like effects in nuclear factor-kappa beta (NFκB) activation. ...
... which accumulates and leads to the inhibition of hypoxia-inducible factor 1α (HIF1α) degradation (inhibition of the HIF prolyl- ... a partially unraveled alpha helix in the semi open form, and an alpha helix in the active form. The mitochondrial form of IDH2 ... It is a homodimer in which each subunit has a Rossmann fold, and a common top domain of interlocking β sheets. Mtb IDH-1 is ... The mitochondrial form of IDH, like most isoforms, is a homodimer, in which two identical monomer subunits form one unit. The ...
The most researched of these targets is hypoxia inducible factor 1a (HIF1a), a transcription factor that induces the expression ... In hypoxic conditions, HIF1A subunits accumulate and bind to HIFB. This heterodimer of HIF is a transcription factor that ... In the normal cell with active VHL protein, HIF alpha is regulated by hydroxylation in the presence of oxygen. When iron, 2- ... Knowles HJ, Raval RR, Harris AL, Ratcliffe PJ (April 2003). "Effect of ascorbate on the activity of hypoxia-inducible factor in ...
... stabilizes transactive hypoxia-inducible factor-1alpha by inhibiting von Hippel-Lindau recruitment and asparagine hydroxylation ... "BRCA1 augments transcription by the NF-kappaB transcription factor by binding to the Rel domain of the p65/RelA subunit". The ... Karetsou Z, Kretsovali A, Murphy C, Tsolas O, Papamarcaki T (April 2002). "Prothymosin alpha interacts with the CREB-binding ... "Transactivation and growth suppression by the gut-enriched Krüppel-like factor (Krüppel-like factor 4) are dependent on acidic ...
Mobasheri A, Richardson S, Mobasheri R, Shakibaei M, Hoyland JA (October 2005). "Hypoxia inducible factor-1 and facilitative ... A helical wheel analysis shows that the membrane-spanning alpha-helices are amphipathic, with one side being polar and the ... glycoprotein-associated/light or catalytic subunits of heterodimeric amino-acid transporters *SLC7A5 ... GLUT1 behaves as a Michaelis-Menten enzyme and contains 12 membrane-spanning alpha helices, each containing 20 amino acid ...
"Hypoxia-inducible C-to-U coding RNA editing downregulates SDHB in monocytes". PeerJ. 1: e152. doi:10.7717/peerj.152. PMC ... Succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial (SDHB) also known as iron-sulfur subunit of complex II ... After birth these cells usually die, a process that is triggered by a decline in nerve growth factor (NGF)which initiates ... PHD action normally requires oxygen and alpha-ketoglutarate as cosubstrates and ferrous iron and ascorbate as cofactors. ...
ERR-alpha complex, which are essential metabolic regulatory transcription factors.[11][12][13][14][15][16] ... cellular response to hypoxia. • triglyceride mobilization. • negative regulation of prostaglandin biosynthetic process. • ... SIRT1 inhibits NF-κB-regulated gene expression by deacetylating the RelA/p65 subunit of NF-κB at lysine 310.[57][58] But NF-κB ... "A fasting inducible switch modulates gluconeogenesis via activator/coactivator exchange". Nature. 456 (7219): 269-73. Bibcode ...
Succinate inhibition of prolyl hydroxylases (PHDs) stabilizes the transcription factor hypoxia inducible factor (HIF)1α.[6][26] ... This enzyme complex is a 4 subunit membrane-bound lipoprotein which couples the oxidation of succinate to the reduction of ... Metabolic signaling involving succinate can be involved in inflammation via stabilization of HIF1-alpha or GPR91 signaling in ... "Inhibition of hypoxia-inducible factor (HIF) hydroxylases by citric acid cycle intermediates: possible links between cell ...
Each subunit has three different structural domains: a short N-terminal epidermal growth factor (EGF) domain; an α-helical ... cellular response to hypoxia. • embryo implantation. • negative regulation of cell proliferation. • prostaglandin metabolic ... "Inducible COX-2 dominates over COX-1 in prostacyclin biosynthesis: Mechanisms of COX-2 inhibitor risk to heart disease". Life ... Allosteric subunit binds a non-substrate, activating FA (e.g., palmitic acid). The allosteric subunit with bound fatty acid ...
One of the major stimuli of angiogenesis is hypoxia, resulting in activation of hypoxia-inducible transcription factors (HIFs) ... Elongation factor 3, A subunit of protein phosphatase 2A and TOR1).[9] Specific protein activators regulate the PIKK kinases ... basic fibroblast growth factor (bFGF), ephrin-B2, vascular enothelial growth factor (VEGF), and members of the tumor growth ... human epidermal growth factor receptor 2) and IGFR (insulin-like growth factor receptor), mutations in PI3K and mutations/ ...
... alpha), and tumour necrosis factor (TNF‑α) indicative of cytokine release syndrome (CRS) suggest an underlying immunopathology ... It includes two subunits: S1 and S2. S1 determines the virus-host range and cellular tropism via the receptor-binding domain. ... Levels of interleukin 1B, interferon-gamma, interferon-inducible protein 10, and monocyte chemoattractant protein 1 were all ... hypoxia, or more than 50% lung involvement on imaging) and 5% of patients suffer critical symptoms (respiratory failure, shock ...
... as it activates of NF-κB as well as hypoxia-inducible factor 1. The head domain of BadA is more complex than other TAAs. It is ... Structure: The neck domain is a homotrimer, where three of the same subunits associate. All three subunits are arranged in such ... Hence, the stalk domains can be considered alpha helical coiled-coils that deviate from the standard model due to their unusual ... In essence, they are virulence factors, factors that make the bacteria harmful and infective to the host organism. TAAs are ...
As a p53 inducible gene, NOXA is transcribed and translated to Noxa in response to DNA damage and hypoxia induced apoptosis. A ... Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) (Figure 5) is a member of the tumor necrosis factor (TNF) ... One of the two molecules of this complex is multimeric alpha lactalbumin (MAL) (Figure 3), which was first discovered during a ... that the mechanisms behind the function of E4orf4 is closely associated with several other proteins including the B55 subunit ...
VHL complex targets member of the hypoxia-inducible transcription factor family (HIF) for degradation by interacting with the ... Bache KG, Raiborg C, Mehlum A, Stenmark H (April 2003). "STAM and Hrs are subunits of a multivalent ubiquitin-binding complex ... alpha} via the N-terminal pathway". The Journal of Biological Chemistry. 285 (51): 40192-200. doi:10.1074/jbc.M110.131615. PMC ... The retinoic acid-inducible gene I (RIG-I) protein is a primary immune system sensor for viral and other invasive RNA in human ...
Hypoxia-inducible factor (HIF)-1α has also been found to interact with hNaa10 to inhibit hNaa10-mediated activation of β- ... NatA is composed of two subunits, the catalytic subunit Naa10 and the auxiliary subunit Naa15. NatA subunits are more complex ... Hole K, Van Damme P, Dalva M, Aksnes H, Glomnes N, Varhaug JE, Lillehaug JR, Gevaert K, Arnesen T (2011). "The human N-alpha- ... NatC complex consists of one catalytic subunit Naa30p and two auxiliary subunits Naa35p and Naa38p. All three subunits are ...
March 2011). "Absence of the Birt-Hogg-Dubé gene product is associated with increased hypoxia-inducible factor transcriptional ... Researchers have shown that FLCN could interact with both subunits in a cilium-dependent manner and localize to cilia in FLCN- ... The DENN domain family of proteins are guanine nucleotide exchange factors (GEFs) for Rab proteins, members of the Ras ... TFE3 and TFEB are members of the microphthalmia-associated transcription factor (MiTF) family, which also includes MiTF and ...
This gene has also been identified as a co-activator of HIF1A (hypoxia-inducible factor 1 alpha), and, thus, plays a role in ... "MRG1 binds to the LIM domain of Lhx2 and may function as a coactivator to stimulate glycoprotein hormone alpha-subunit gene ... "Structural basis for recruitment of CBP/p300 by hypoxia-inducible factor-1 alpha". Proc. Natl. Acad. Sci. U.S.A. 99 (8): 5367- ... "The TRAP/Mediator coactivator complex interacts directly with estrogen receptors alpha and beta through the TRAP220 subunit and ...
MET transcription is activated by hypoxia-inducible factor 1 (HIF1), which is activated by low concentration of intracellular ... The primary single chain precursor protein is post-translationally cleaved to produce the alpha and beta subunits, which are ... "Hypoxia-inducible factor-dependent degeneration, failure, and malignant transformation of the heart in the absence of the von ... "Hepatocyte growth factor/scatter factor activates the ETS1 transcription factor by a RAS-RAF-MEK-ERK signaling pathway". ...
Succinate inhibition of prolyl hydroxylases (PHDs) stabilizes the transcription factor hypoxia inducible factor (HIF)1α. PHDs ... This enzyme complex is a 4 subunit membrane-bound lipoprotein which couples the oxidation of succinate to the reduction of ... The GABA shunt serves as an alternate route to convert alpha-ketoglutarate into succinate, bypassing the TCA cycle intermediate ... "Inhibition of hypoxia-inducible factor (HIF) hydroxylases by citric acid cycle intermediates: possible links between cell ...
This catalytic subunit is not present in the immunoproteasome and is replaced by catalytic inducible subunit beta1i (proteasome ... This protein is one of the 17 essential subunits (alpha subunits 1-7, constitutive beta subunits 1-7, and inducible subunits ... "Proteomic analysis reveals that proteasome subunit beta 6 is involved in hypoxia-induced pulmonary vascular remodeling in rats ... Accordingly, gene expression by degradation of transcription factors, such as p53, c-Jun, c-Fos, NF-κB, c-Myc, HIF-1α, MATα2, ...
This gene encodes the alpha subunit of transcription factor hypoxia-inducible factor-1 (HIF-1), which is a heterodimer composed ... alpha subunit (basic helix-loop-helix transcription factor). hypoxia-inducible factor1alpha. member of PAS protein 1. member of ... hypoxia inducible factor 1 subunit alphaprovided by HGNC. Primary source. HGNC:HGNC:4910 See related. Ensembl:ENSG00000100644 ... hypoxia-inducible factor 1-alpha. Names. ARNT interacting protein. PAS domain-containing protein 8. basic-helix-loop-helix-PAS ...
Role of hypoxia-inducible factor (HIF)-1alpha versus HIF-2alpha in the regulation of HIF target genes in response to hypoxia, ... The forkhead transcription factor FOXO4 induces the down-regulation of hypoxia-inducible factor 1 alpha by a von Hippel-Lindau ... pVHL functions in a multi-subunit E3 ubiquitin ligase that targets the hypoxia-inducible transcription factor Hif1 alpha for ... Bimodal effect of hypoxia in cancer: role of hypoxia inducible factor in apoptosis. Wang, Y., Pakunlu, R.I., Tsao, W., Pozharov ...
R-BTA-1234176. Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha. R-BTA-5689880. Ub-specific processing ... R-BTA-1234176. Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha. R-BTA-5689880. Ub-specific processing ... R-BTA-1234162. Oxygen-dependent asparagine hydroxylation of Hypoxia-inducible Factor Alpha. ... R-BTA-1234162. Oxygen-dependent asparagine hydroxylation of Hypoxia-inducible Factor Alpha. ...
... alpha subunit in the Definitions.net dictionary. Meaning of hypoxia-inducible factor 1, alpha subunit. What does hypoxia- ... alpha subunit mean? Information and translations of hypoxia-inducible factor 1, alpha subunit in the most comprehensive ... alpha subunit. Here are all the possible meanings and translations of the word hypoxia-inducible factor 1, alpha subunit.. ... alpha Subunit. Hypoxia-inducible factor 1, alpha subunit is a basic helix-loop-helix transcription factor that is regulated by ...
This gene encodes the alpha subunit of transcription factor hypoxia-inducible factor-1 (HIF-1), which is a heterodimer composed ... hypoxia-inducible factor asparagine hydroxylase , peptide-aspartate beta-dioxygenase , hypoxia-inducible factor 1, alpha ... alpha Subunit Inhibitor (HIF1AN) * Hypoxia Inducible Factor 1, alpha Subunit Inhibitor (HIF1AN) ... alpha subunit inhibitor S homeolog (hif1an.S) anticorps * hypoxia inducible factor 1 alpha subunit inhibitor (Hif1an) anticorps ...
Hypoxia Inducible Factor 1 Alpha Subunit, including: function, proteins, disorders, pathways, orthologs, and expression. ... This gene encodes the alpha subunit of transcription factor hypoxia-inducible factor-1 (HIF-1), which is a heterodimer composed ... Hypoxia Inducible Factors (HIFs) are transcription factors that are activated in response to decreased oxygen availability in ... Hypoxia Inducible Factor 1 Alpha Subunit 2 3 5 * Hypoxia Inducible Factor 1, Alpha Subunit (Basic Helix-Loop-Helix ...
... alpha Subunit/genetics. *Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ... Over-expression of hypoxia-inducible factor-1alpha increases the invasive potency of LNCaP cells in vitro.. Luo Y1, He DL, Ning ... To evaluate the effect of hypoxia-inducible factor-1alpha (HIF-1alpha) over-expression on the invasion-associated proteins in ... as HIF-1alpha is a transcriptional factor that could activate genes involved in the response to hypoxia, but might also enhance ...
Here we report that a molecular mechanism possibly contributing to these functions of HGF may be hypoxia inducible factor-1 ( ... Hepatocyte growth factor (HGF) plays an important role in tumor growth and progression also by regulating invasive/metastatic ... alpha Subunit * JNK Mitogen-Activated Protein Kinases* * MAP Kinase Kinase 4 * Mitogen-Activated Protein Kinase Kinases / ... Here we report that a molecular mechanism possibly contributing to these functions of HGF may be hypoxia inducible factor-1 ( ...
... sequences generally contain one or more binding sites for a heterodimeric DNA binding complex termed hypoxia-inducible factor-1 ... to hypoxia and demonstrate the operation of HIF-1alpha-dependent and HIF-1alpha-independent pathways of hypoxia-inducible gene ... hypoxia-inducible expression was critically dependent on HIF-1alpha, whereas for other genes (e.g. heme oxygenase-1) hypoxia- ... Comparison of hypoxia-inducible gene expression in wild type, HIF-1alpha-defective, and HIF-1alpha-complemented cells revealed ...
The aim of this work was to evaluate the effects of semaphorin 3A (Sema3A) and hypoxia inducible factor 1 subunit alpha (HIF1α ... Semaphorin 3A-hypoxia inducible factor 1 subunit alpha co-overexpression enhances the osteogenic differentiation of induced ... Semaphorin 3A-hypoxia inducible factor 1 subunit alpha co-overexpression enhances the oste ... factors may represent a promising strategy to optimize tissue engineering-based strategy in bone repair. ...
... definition of regulatory domains within the alpha subunit. J Biol Chem 272:11205-11214. ... The hypoxia-induced upregulation of EPO expression is regulated at the transcriptional level by the hypoxia inducible factor ( ... 1995) Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc Natl Acad ... 2000) Hypoxia-inducible factor-1α is a positive factor in solid tumor growth. Cancer Res 60:4010-4015. ...
High levels of hypoxia-inducible transcription factors (HIF) are particularly important in the clear cell type of kidney cancer ... alpha Subunit / biosynthesis* * Hypoxia-Inducible Factor 1, alpha Subunit / genetics ... pVHL targets α-subunits of hypoxia-inducible transcription factors (HIF) for proteasomal degradation. The two main HIF-α ... Hypoxia, Hypoxia-inducible Transcription Factors, and Renal Cancer Eur Urol. 2016 Apr;69(4):646-657. doi: 10.1016/j.eururo. ...
Hydroxylates HIF-1 alpha at Asn-799 in the C-terminal transactivation domain (CAD). Functions as an oxygen sensor and, under ... normoxic conditions, the hydroxylation prevents interaction of HIF-1 with transcriptional coactivators including Cbp/p300- ... help/subunit_structure target=_top>More...,/a>,/p>Subunit structurei. Homodimer; homodimerization is essential for catalytic ... Hypoxia-inducible factor-L-asparagine + 2-oxoglutarate + O2 = hypoxia-inducible factor-(3S)-3-hydroxy-L-asparagine + succinate ...
... to strains expressing Cre recombinase in various tissues and may be useful for studies of the role of HIF transcription factors ... The hypoxia-inducible factor alpha pathway couples angiogenesis to osteogenesis during skeletal development. J Clin Invest 117( ... alpha subunit. Gene Synonym(s). AA959795; HIF-1-alpha; HIF-1A; HIF-1alpha; HIF1; HIF1-ALPHA; HIF1alpha; MOP1; PASD8; bHLHe78; ... Hypoxia-inducible factor-1alpha is a positive factor in solid tumor growth. Cancer Res 60(15):4010-5. PubMed: 10945599MGI: J: ...
... as seen with the loss of markers OCT3/4 and TRA-1-81 - and tumorigenicity. However, these iPS-MSCs are still positive for ... Semaphorin 3A-hypoxia inducible factor 1 subunit alpha co-overexpression enhances the osteogenic differentiation of induced ... heat-inactivated FBS in alpha MEM medium followed by CD73-based FACS21. The efficiency of CD73 positive cells achieved by their ... Increase expression of osteoblast markers, the transcription factor Runx2, alkaline phosphatase (ALP), extracellular matrix and ...
hypoxia-inducible factor 1, alpha subunit inhibitor. 38. 6. 9. 4. Sequence references in MGI J:259852 Mouse Genome Informatics ...
Hypoxia-Inducible Factor 1, alpha Subunit / antagonists & inhibitors*, metabolism. Liver Neoplasms / drug therapy*, metabolism ... alpha Subunit; 0/NF-kappa B; 0/Phenylurea Compounds; 0/Piperidones; 0/sorafenib; 25X51I8RD4/Niacinamide; EC 6.3.2.19/Von Hippel ... Hypoxia-mediated sorafenib resistance can be overcome by EF24 through Von Hippel-Lindau tumor suppressor-dependent HIF-1α ... CONCLUSION: Hypoxia induced by sustained sorafenib treatment confers sorafenib resistance to HCC through HIF-1α and NF-κB ...
Adaptation to hypoxia is mediated by transactivation of hypoxia-responsive genes by hypoxia-inducible factor-1 (HIF-1) in ... CH1 has a triangular geometry composed of four alpha-helices with three intervening Zn(2+)-coordinating centers. CH1 serves as ... Adaptation to hypoxia is mediated by transactivation of hypoxia-responsive genes by hypoxia-inducible factor-1 (HIF-1) in ... hypoxia inducible factor-1 alpha subunit. A. 42. Homo sapiens. Mutation(s): 0 Gene Names: hypoxia inducible factor-1 alpha, ...
... or other studies where imaging/reporting the development of tissue hypoxia and the action of small molecule inhibitors of HIF ... bioluminescent reporter mice may be useful in researching transcriptional regulation of hypoxia-inducible genes, cancer, ... The human hypoxia-inducible factor 1 alpha sequence coding for amino acids 530-652, including the C-terminal portion of the ... A fusion protein was created with a human hypoxia-inducible factor 1 alpha sequence coding for amino acids 530-652 (HIF1a [aa ...
Hypoxia-Inducible Factor 1 alpha subunit. IDH1 protein human. Immunohistochemistry. Mutation/genetics. Real-time polymerase ...
1998) Molecular characterization and chromosomal localization of a third alpha-class hypoxia inducible factor subunit, ... 1997) A novel bHLH-PAS factor with close sequence similarity to hypoxia-inducible factor 1α regulates the VEGF expression and ... 2007) Hypoxia inducible factor (HIF) function in innate immunity and infection. J Mol Med (Berl) 85(12):1339-1346. ... 2011) Hypoxia-inducible factor 1 is a master regulator of breast cancer metastatic niche formation. Proc Natl Acad Sci USA 108( ...
0 (HIF1A protein, human); 0 (Hypoxia-Inducible Factor 1, alpha Subunit); 0 (Matrix Metalloproteinase Inhibitors); EC 1.14.11 ... revealed that Aldolase A-driven lung cancer metastasis was closely linked to hypoxia inducible factor 1 alpha (HIF-1α)- ... Subunidade alfa do Fator 1 Induz vel por Hip xia/metabolismo. Neoplasias Pulmonares/enzimologia. Metaloproteinase 9 da Matriz/ ... Class II fructose-1,6-bisphosphate aldolases (FBA-II) are attractive new targets for the discovery of drugs to combat invasive ...
Hypoxia-Inducible Factor 1, alpha Subunit); 0 (LAMP2 protein, human); 0 (Lysosomal-Associated Membrane Protein 2); 0 (Proto- ... Epidermal growth factor receptor overexpression in human cancer can be effectively targeted by drugs acting as specific ... A phase-I study of lapatinib in combination with foretinib, a c-MET, AXL and vascular endothelial growth factor receptor ... Foretinib is an inhibitor of c-Met, VEGF receptor 2 (VEGFR-2), platelet-derived growth factor receptor beta (PDGFRB), AXL, Fms- ...
... which are independent factors for adverse cardiovascular outcomes. We hypothesized that decreased blood pressure by ... Hypoxia-Inducible Factor 1, alpha Subunit / biosynthesis. Kidney / blood supply. Microvessels / pathology, physiology*. ... alpha Subunit; EC 1.14.11.2/Procollagen-Proline Dioxygenase; EC 6.3.2.19/Von Hippel-Lindau Tumor Suppressor Protein ... These were accompanied by increased myocardial expression of hypoxia-inducible factor (HIF)-1α, inflammation, and microvascular ...
... alpha subunit (basic helix-loop-helix transcription factor) [Source:HGNC. Mouse Orthologue:. Hif1a. Mouse Description:. hypoxia ... hypoxia-inducible factor 1-alpha [Source:RefSeq peptide;Acc:NP_956527]. Human Orthologue:. HIF1A. Human Description:. hypoxia ... alpha subunit Gene [Source:MGI Symbol;Acc:MGI:106918]. ...
Tumor Necrosis Factor-alpha. *Hypoxia-Inducible Factor 1, alpha Subunit. *Shock. *Shock, Septic ... During hypoxia, the low availability of oxygen limits the reaction; HIF-1α is no. longer degraded and rapidly accumulates and ... growth factor (VEGF) and erythropoietin. Under hypoxic conditions, HIF mediates also a. decrease in mRNA levels of the ... ATP due to impaired mitochondrial function may be a factor in modulating the immune response. in sepsis. Alterations in ...
Plasmid pcDNA3 mHIF-1α MYC (P402A/P577A/N813A) from Dr. Celeste Simons lab contains the insert mHIF-1α (P402A/P577A/N813A) and ... The N-terminal transactivation domain confers target gene specificity of hypoxia-inducible factors HIF-1alpha and HIF-2alpha. ... alpha subunit * Alt name. HIF1alpha * Species. M. musculus (mouse) ... A 10-amino-acid c-myc tag was further inserted at the C terminus of the HIF-1α cDNAs by using a Pfu-PCR-based protocol. The ...
Hypoxia-Inducible Factor 1, alpha Subunit. 2. 2018. 616. 0.750. Why? Inflammatory Bowel Diseases. 3. 2019. 1673. 0.730. Why? ... Interleukin-2 Receptor alpha Subunit. 7. 2015. 278. 1.110. Why? Crohn Disease. 6. 2018. 1930. 0.990. Why? ... Suppressor Factors, Immunologic. 1. 2012. 73. 0.140. Why? Reverse Transcriptase Polymerase Chain Reaction. 2. 2016. 5362. 0.140 ... Basic Helix-Loop-Helix Transcription Factors. 1. 2018. 1091. 0.530. Why? CD4-Positive T-Lymphocytes. 8. 2016. 4025. 0.530. Why ...
Dann C.E. III, Bruick R.K., Deisenhofer J. (2002). Structure of factor-inhibiting hypoxia-inducible factor 1: an asparaginyl ... Webb J.D., Muranyi A., Pugh C.W., Ratcliffe P.J., Coleman M.L. (2009). MYPT1, the targeting subunit of smooth-muscle myosin ... is a substrate for the asparaginyl hydroxylase factor inhibiting hypoxia-inducible factor (FIH).. Biochem. J. 420. с. 327 - 333 ... HIF1AN, FIH1, hypoxia inducible factor 1 alpha subunit inhibitor. Зовнішні ІД. MGI: 2442345 HomoloGene: 9906 GeneCards: HIF1AN ...
Dann CE, Bruick RK, Deisenhofer J (2003). "Structure of factor-inhibiting hypoxia-inducible factor 1: An asparaginyl ... alpha subunit inhibitor". CS1 maint: discouraged parameter (link) Lando D, Peet DJ, Whelan DA, Gorman JJ, Whitelaw ML (2002). " ... "Hypoxia-inducible factor (HIF) asparagine hydroxylase is identical to factor inhibiting HIF (FIH) and is related to the cupin ... "Structure of factor-inhibiting hypoxia-inducible factor (HIF) reveals mechanism of oxidative modification of HIF-1 alpha". J. ...
  • HIF-1 functions as a master regulator of cellular and systemic homeostatic response to hypoxia by activating transcription of many genes, including those involved in energy metabolism, angiogenesis, apoptosis, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia. (nih.gov)
  • Functions as a master transcriptional regulator of the adaptive response to hypoxia. (genecards.org)
  • To evaluate the effect of hypoxia-inducible factor-1alpha (HIF-1alpha) over-expression on the invasion-associated proteins in human prostate cancer cells, as HIF-1alpha is a transcriptional factor that could activate genes involved in the response to hypoxia, but might also enhance the invasive potency of prostate cancer cells. (nih.gov)
  • HIF1A is a basic helix-loop-helix PAS domain containing protein, and is considered as the master transcriptional regulator of cellular and developmental response to hypoxia. (wikipedia.org)
  • One of the most important factors in the cellular response to hypoxia is hypoxia-inducible factor (HIF), which transcriptionally activates genes encoding proteins that mediate adaptive responses to reduced oxygen availability. (acris-antibodies.com)
  • Overexpression of PNUTS markedly increased cell death in response to hypoxia, with increased expression of Bax, an apoptosis-related gene induced by p53. (thebiogrid.org)
  • HIF1a localizes in cytoplasm in normoxia, but it can translocate into nuclear in response to hypoxia. (ptglab.com)
  • In response to hypoxia, cells undergo specific alterations in gene expression patterns geared to promote cell survival and maintain homeostasis. (asm.org)
  • Although several transcription programs are activated in response to hypoxia, the hypoxia-inducible factors (HIFs) regulate a critical repertoire of genes, making them central regulators of the cellular response to hypoxia ( 10 , 34 ). (asm.org)
  • Several hundred genes are induced in response to hypoxia, and a great deal of research has been focused on identifying direct HIF target genes ( 34 ). (asm.org)
  • Furthermore, numerous genes involved in hematopoietic functions, including erythropoiesis and immunoregulation, were differentially expressed in response to hypoxia. (bvsalud.org)
  • Hypoxia inducible factors (HIFs) are transcription factors that mediate the cellular response to hypoxia. (nature.com)
  • Hypoxia Inducible Factor 1 (HIF1) is the most important transcription factor in the tumor response to hypoxia since the survival and adaptation of tumor cells to low oxygen levels depends upon the expression of this transcription factor and its family members [ 1 , 2 ]. (omicsonline.org)
  • Hypoxia-inducible factor-1α mediates the expression of mature β cell-disallowed genes in hypoxia-induced β cell dedifferentiation. (nih.gov)
  • Under hypoxic conditions, activates the transcription of over 40 genes, including erythropoietin, glucose transporters, glycolytic enzymes, vascular endothelial growth factor, HILPDA, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia. (genecards.org)
  • Here we report that a molecular mechanism possibly contributing to these functions of HGF may be hypoxia inducible factor-1 (HIF-1)-dependent expression of genes of the plasminogen activation system. (nih.gov)
  • In this study, we sought to determine the differential roles of HIF-1α and HIF-2α in the regulation of the hypoxia-induced expression of EPO as well as other oxygen-regulated genes in cultured cortical astrocytes. (jneurosci.org)
  • Hypoxia-inducible expression has been demonstrated for many groups of mammalian genes, and studies of transcriptional control have revealed the existence of hypoxia-responsive elements (HREs) in the cis-acting sequences of several of these genes. (ox.ac.uk)
  • To analyze this response further, Chinese hamster ovary cells were stably transfected with plasmids bearing HREs linked to genes encoding immunoselectable cell surface markers, and clones that showed reduced or absent hypoxia-inducible marker expression were selected from a mutagenized culture of cells. (ox.ac.uk)
  • For some genes (e.g. glucose transporter-1), hypoxia-inducible expression was critically dependent on HIF-1alpha, whereas for other genes (e.g. heme oxygenase-1) hypoxia-inducible expression appeared largely independent of the expression of HIF-1alpha. (ox.ac.uk)
  • Adaptation to hypoxia is mediated by transactivation of hypoxia-responsive genes by hypoxia-inducible factor-1 (HIF-1) in complex with the CBP and p300 transcriptional coactivators. (rcsb.org)
  • Hypoxia-inducible factor 1 (HIF-1) activates transcription of genes encoding proteins that play key roles in breast cancer biology. (pnas.org)
  • We report that the histone demethylase jumonji domain containing protein 2C (JMJD2C) selectively interacts with HIF-1α, but not HIF-2α, and that HIF-1α mediates recruitment of JMJD2C to the hypoxia response elements of HIF-1 target genes. (pnas.org)
  • Taken together, these findings establish an important epigenetic mechanism that stimulates HIF-1-mediated transactivation of genes encoding proteins involved in metabolic reprogramming and lung metastasis in breast cancer. (pnas.org)
  • HIF-1α (or HIF-2α) dimerizes with HIF-1β, and the heterodimer binds to DNA at sites containing the consensus nucleotide sequence 5′-RCGTG-3′ within the hypoxia response element (HRE) of target genes to activate transcription ( 15 ). (pnas.org)
  • More than 1,000 genes have been identified as HIF target genes, many of which are transactivated by both HIF-1 and HIF-2 ( 1 , 16 ). (pnas.org)
  • However, HIF-1 and HIF-2 each also controls a battery of unique target genes. (pnas.org)
  • These "ODD-Luc" bioluminescent reporter mice may be useful in researching transcriptional regulation of hypoxia-inducible genes, cancer, ischemia, cardiovascular, myocardial infarction, stroke, pharmacokinetics, or other studies where imaging/reporting the development of tissue hypoxia and the action of small molecule inhibitors of HIF prolyl hydroxylase activity are appropriate. (jax.org)
  • HIF-1α is no longer degraded and rapidly accumulates and triggers the transcription of genes involved in oxygen homeostasis such as glycolytic enzymes, glucose transporters, vascular endothelial growth factor (VEGF) and erythropoietin. (knowcancer.com)
  • Identification of Key HIF-1α Target Genes that Regulate Adaptation to Hypoxic Conditions in Tibetan Chicken Embryos. (bioportfolio.com)
  • Among these genes, HIF-1α, TNFα and MMP9 are specifically inhibited, expression of THBS2 was up-regulated. (biomedcentral.com)
  • Our results revealed important interactions among transcription factors and offer a multifactorial perspective of genes involved in seawater acclimation. (biomedcentral.com)
  • Hypoxia inducible factor-1α (HIF-1α) is an essential regulator of the cellular response to low oxygen concentrations, activating a broad range of genes that provide adaptive responses to oxygen deprivation. (nih.gov)
  • HIF-1 is known to induce transcription of more than 60 genes, including VEGF and erythropoietin that are involved in biological processes such as angiogenesis and erythropoiesis, which assist in promoting and increasing oxygen delivery to hypoxic regions. (wikipedia.org)
  • HIF-1 also induces transcription of genes involved in cell proliferation and survival, as well as glucose and iron metabolism. (wikipedia.org)
  • In accordance with its dynamic biological role, HIF-1 responds to systemic oxygen levels by undergoing conformational changes, and associates with HRE regions of promoters of hypoxia-responsive genes to induce transcription. (wikipedia.org)
  • however, under hypoxia, HIF1A protein degradation is prevented and HIF1A levels accumulate to associate with HIF1B to exert transcriptional roles on target genes Enzymes prolyl hydroxylase (PHD) and HIF prolyl hydroxylase (HPH) are involved in specific post-translational modification of HIF1A proline residues (P402 and P564 within the ODD domain), which allows for VHL association with HIF1A. (wikipedia.org)
  • Examples of HIF target genes include VEGF, glucose transporter 1 (GLUT1), and EPO. (acris-antibodies.com)
  • HIF binds to the hypoxia-responsive element, which contains the core recognition sequence 5'-TACGTG-3', in the cis-regulatory regions of hypoxia-inducible genes. (acris-antibodies.com)
  • Although 3p loss was determined by evaluating 12 genes located in 3p14.2, it remains unclear which factor encoded on 3p is responsible for the interaction with TP53. (springermedizin.de)
  • In zebrafish, the expression changes for Hif-1α and Hif-3α observed during development and under environmental stress conditions do not support this hypothesis, and recent studies indicate that Hif-3α is also able to directly control transcriptional activity of certain genes. (zfin.org)
  • This is supported by the fact that some of the downstream genes of the Hif signaling pathway, namely, erythropoietin and vascular endothelial growth factor , are known to be clock controlled as well. (zfin.org)
  • Recent studies have shown that the histone demethylase genes JMJD1A , JMJD2B , and JARID1B are HIF targets, suggesting that HIFs indirectly influence gene expression at the level of histone methylation under hypoxia. (asm.org)
  • In this study, we identify a subset of hypoxia-inducible genes that are dependent on JMJD1A in both renal cell and colon carcinoma cell lines. (asm.org)
  • Under hypoxic conditions, HIF-α protein is stabilized, translocates to the nucleus, dimerizes with ARNT, and binds hypoxia-responsive elements (HREs) in the regulatory regions of target genes ( 51 ). (asm.org)
  • HIF-1α and HIF-2α will bind the same sequences in cells but do not have completely overlapping abilities to regulate genes ( 5 , 17 , 44 ). (asm.org)
  • Table 1 List of genes examined in this study. (biomedcentral.com)
  • A mitoscriptome profiling study demonstrated alteration in several genes related to mitochondria, consistent with the mitochondrial functional decline observed after trauma hemorrhage (T-H). Our experiments led to the identification of sirtuin 1 (SIRT1) as a potential target in T-H. Administration of resveratrol (a naturally occurring polyphenol and activator of SIRT1) after T-H improved left ventricular function and tissue ATP levels. (springer.com)
  • p300/CBP-HIF complexes participate in the induction of hypoxia-responsive genes, including VEGF. (fishersci.com)
  • Multivariate analyses revealed that smolt stage, water salinity, and morbidity status were relevant factors to consider with the expression of these genes in relation to hypoxic stress. (g3journal.org)
  • These hypoxia candidate genes will be put into application screening Chinook salmon to determine the identity of stressors impacting the fish. (g3journal.org)
  • We aimed to evaluate whether the frequency of three polymorphisms in hypoxia-induced factor-1α (HIF-1α), vascular endothelial growth factor A (VEGFA), and KDR (encoding vascular endothelial growth factor receptor 2) genes was higher in alcoholics presenting liver disease (ALD) and ALD patients who developed HCC. (cdc.gov)
  • Over 50 genes are inducible by hypoxia, via hypoxia inducible factor 1alpha (HIF-1alpha). (ox.ac.uk)
  • Carbonic anhydrase IX (CAIX) is one of the most inducible and most uniformly induced genes and because of its stability and membrane location provides a reliable histochemical marker of hypoxia. (ox.ac.uk)
  • HIF1A (Hypoxia Inducible Factor 1 Alpha Subunit) is a Protein Coding gene. (genecards.org)
  • Diseases associated with HIF1A include Hypoxia and Retinal Ischemia . (genecards.org)
  • These mice have the C-terminal portion of the hypoxia-inducible factor 1 alpha ( HIF1A ) oxygen-dependent degradation domain (ODD) fused to the firefly luciferase ( luc ) gene. (jax.org)
  • Hypoxia-inducible factor 1-alpha, also known as HIF-1-alpha, is a subunit of a heterodimeric transcription factor hypoxia-inducible factor 1 (HIF-1) that is encoded by the HIF1A gene. (wikipedia.org)
  • The dysregulation and overexpression of HIF1A by either hypoxia or genetic alternations have been heavily implicated in cancer biology, as well as a number of other pathophysiologies, specifically in areas of vascularization and angiogenesis, energy metabolism, cell survival, and tumor invasion. (wikipedia.org)
  • HIF1 is a heterodimeric basic helix-loop-helix structure that is composed of HIF1A, the alpha subunit (this protein), and the aryl hydrocarbon receptor nuclear translocator (Arnt), the beta subunit. (wikipedia.org)
  • The human HIF1A gene encodes for the alpha subunit, HIF1A of the transcription factor hypoxia-inducible factor (HIF1). (wikipedia.org)
  • In most cells, HIF1A gene is constitutively expressed in low levels under normoxic conditions, however, under hypoxia, HIF1A transcription is often significantly upregulated. (wikipedia.org)
  • In hypoxia-independent ways, HIF1A expression may be upregulated through a redox-sensitive mechanism. (wikipedia.org)
  • The hydroxylation of HIF1A proline residue also regulates its ability to associate with co-activators under hypoxia. (wikipedia.org)
  • This assay has high sensitivity and excellent specificity for detection of Hypoxia Inducible Factor 1 Alpha (HIF1a). (mybiosource.com)
  • No significant cross-reactivity or interference between Hypoxia Inducible Factor 1 Alpha (HIF1a) and analogues was observed. (mybiosource.com)
  • 3 samples with low, middle and high level Hypoxia Inducible Factor 1 Alpha (HIF1a) were tested 20 times on one plate, respectively. (mybiosource.com)
  • 3 samples with low, middle and high level Hypoxia Inducible Factor 1 Alpha (HIF1a) were tested on 3 different plates, 8 replicates in each plate. (mybiosource.com)
  • MBS2702491 is a ready-to-use microwell, strip plate Double-antibody Sandwich ELISA (enzyme-linked immunosorbent assay) Kit for analyzing the presence of the Hypoxia Inducible Factor 1 Alpha (HIF1a) ELISA Kit target analytes in biological samples. (mybiosource.com)
  • The microtiter plate provided in this kit has been pre-coated with an antibody specific to Hypoxia Inducible Factor 1 Alpha (HIF1a). (mybiosource.com)
  • Untreated and cobalt chloride treated HeLa and HepG2 cells were subjected to SDS-PAGE followed by western blot with 66730-1-Ig (HIF1a antibody) at dilution of 1:10000 incubated at room temperature for 1.5 hours. (ptglab.com)
  • Immunofluorescent analysis of (-20°C Ethanol) fixed Cobalt Chloride treated HeLa cells using 66730-1-Ig (HIF1a antibody) at dilution of 1:50 and Alexa Fluor 488-Conjugated AffiniPure Goat Anti-Mouse IgG(H+L). (ptglab.com)
  • 66730-1-Ig targets HIF1a in WB, IHC, IF,ELISA applications and shows reactivity with Human samples. (ptglab.com)
  • Immunofluorescent analysis of (-20°C Acetone) fixed Cobalt Chloride treated HeLa cells (left) and untreaed cell (right) using 20960-1-AP (HIF1a antibody) at dilution of 1:100 and Alexa Fluor 488-conjugated AffiniPure Goat Anti-Rabbit IgG(H+L). (ptglab.com)
  • Immunohistochemical analysis of paraffin-embedded human thyroid cancer using 20960-1-AP (HIF1A antibody) at dilution of 1:50 (under 40x lens). (ptglab.com)
  • 1X10^6 HeLa cells were stained with 0.2ug HIF1a antibody (20960-1-AP, red) and control antibody (blue). (ptglab.com)
  • The report provides comprehensive information on the Hypoxia Inducible Factor 1 Alpha (ARNT Interacting Protein or Basic Helix Loop Helix PAS Protein MOP1 or Class E Basic Helix Loop Helix Protein 78 or Member Of PAS Protein 1 or PAS Domain Containing Protein 8 or HIF1A) , targeted therapeutics, complete with analysis by indications, stage of development, mechanism of action (MoA), route of administration (RoA) and molecule type. (researchandmarkets.com)
  • HIF1-alpha (HIF1A) is a subunit of HIF1, which is a transcription factor found in mammalian cells cultured under reduced oxygen tension. (fishersci.com)
  • Hypoxia Inducible Factors (HIFs) are transcription factors that are activated in response to decreased oxygen availability in the cellular environment. (genecards.org)
  • pVHL targets α-subunits of hypoxia-inducible transcription factors (HIF) for proteasomal degradation. (nih.gov)
  • High levels of hypoxia-inducible transcription factors (HIF) are particularly important in the clear cell type of kidney cancer, in which they are no longer properly regulated by the von Hippel-Lindau protein. (nih.gov)
  • Mice from this strain can be crossed to strains expressing Cre recombinase in various tissues and may be useful for studies of the role of HIF transcription factors in von Hippel-Landau syndrome, adult erythropoiesis, inflammation, mammary epithelium, tumor angiogenesis, and lung development as examples. (jax.org)
  • When bred to a strain with the targeted null allele in von Hippel-Lindau syndrome homolog, Vhlh (Stock No. 004081 ) and a strain expressing Cre recombinase in liver (Stock No. 003574 ), this mutant mouse strain may be useful in the role of HIF transcription factors in von Hippel-Landau syndrome. (jax.org)
  • HIFs are heterodimeric transcription factors, consisting of α and β subunits ( 8 ). (pnas.org)
  • 50 transiently up-regulated transcription factors selected via co-expression correlation and GO selection, five transcription factors, including CEBPB and CEBPD, were confirmed by quantitative PCR to be specific to hyperosmotic stress, while others were also up-regulated after freshwater control transfer, including some well-known osmotic-stress transcription factors such as SGK1 and TSC22D3/Ostf1. (biomedcentral.com)
  • Protein interaction networks suggest a high degree of overlapping among the signaling of transcription factors that respond to osmotic and general stresses, which sheds light on the interpretation of their roles during hyperosmotic stress and emergency. (biomedcentral.com)
  • Cells respond to hypoxia through alterations in gene expression, mediated most notably through the hypoxia-inducible factor (HIF) class of transcription factors. (nih.gov)
  • The hypoxia-inducible transcription factors (HIFs) directly and indirectly mediate cellular adaptation to reduced oxygen tensions. (asm.org)
  • HIF-1 is a heterodimer consisting of an alpha and beta subunit, both belonging to the basic-helix-loop-helix Per-aryl hydrocarbon receptor nuclear translocator-Sim (PAS) family of transcription factors. (fishersci.com)
  • Cellular signalling of oestrogens is triggered by oestrogen receptors (ERs) α (ERα) and β (ERβ) which are the members of nuclear receptor superfamily (NR) of transcription factors (Christoforou et al. (springeropen.com)
  • Hypoxia-inducible factor 1, alpha subunit is a basic helix-loop-helix transcription factor that is regulated by OXYGEN availability and is targeted for degradation by VHL TUMOR SUPPRESSOR PROTEIN. (definitions.net)
  • GO annotations related to this gene include transcription factor activity, sequence-specific DNA binding and protein heterodimerization activity . (genecards.org)
  • Expression of mtHIF-2α but not mtHIF-1α in normoxic astrocytes resulted in a significant upregulation of EPO mRNA and protein. (jneurosci.org)
  • Currently, three HIF-α subunits [HIF-1α, HIF-2α/endothelial PAS domain protein 1 (EPAS-1), and HIF-3α], as well as three HIF-β subunits (HIF-1β/ARNT1, ARNT2, and ARNT3) are known. (jneurosci.org)
  • The von Hippel-Lindau tumor suppressor protein binds to prolyl hydroxylated HIF-α subunits and promotes their ubiquitination and degradation in the 26 S proteasome ( 14 ). (pnas.org)
  • Under hypoxia, proline hydroxylation is impaired and ubiquitination is attenuated, resulting in stabilization of the fusion protein and high levels of luciferase fluorescence in the hypoxic tissue(s). (jax.org)
  • Hypoxia-inducible factor 1-alpha inhibitor is a protein that in humans is encoded by the HIF1AN gene. (wikipedia.org)
  • Its protein expression level can be measured by antibodies against HIF-1-alpha through various biological detection methods including western blot or immunostaining. (wikipedia.org)
  • Transcriptional activation by HIF is linked to its ability to recruit coactivator proteins such as CREB-binding protein (CBP), p300, steroid receptor coactivator-1, and translation initiation factor 2. (acris-antibodies.com)
  • Interestingly, the S. triloba inhibited the expression of VEGF at the mRNA and protein and the HIF-1α mRNA in the MCF 7 breast cancer cells under both normoxic and hypoxic conditions. (biomedcentral.com)
  • Under normoxic condition, HIF-1α rapidly decreases since it is bound to the tumour suppressor Von Hippel-Lindau (VHL) protein, which in turn results in HIF-1α ubiquitynation and becomes a target for the proteosome. (biomedcentral.com)
  • Protein phosphatase 1 nuclear targeting subunit is a hypoxia inducible gene: its role in post-translational modification of p53 and MDM2. (thebiogrid.org)
  • Hypoxia significantly increased mRNA and protein expression of PNUTS in various cell lines concomitantly with increases in p53. (thebiogrid.org)
  • In addition, accumulation of Hif-1α protein during short-term hypoxia was found to depend on the time within the daily light and dark cycle at which hypoxia was encountered, suggesting that the hypoxia signaling pathway may be regulated by the circadian clock. (zfin.org)
  • In this study, we evaluated the activity of SIRT1, a mitochondrial functional modulator, and the mitochondrial-glycolytic balance after T-H. We determined the changes in protein levels of pyruvate dehydrogenase kinase (PDK)-1 and nuclear c-Myc, peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α and NF-E2-related factor (NRF)2 after T-H and after treatment with resveratrol or a combination of sirtinol (a SIRT1 inhibitor) and resveratrol. (springer.com)
  • Western Blot: RhoA Antibody [NB100-91273] - Rat spinal cord lysate using Rabbit antibody to Transforming protein RhoA: whole serum at 1:2000 dilution. (novusbio.com)
  • Disclaimer note: The observed molecular weight of the protein may vary from the listed predicted molecular weight due to post translational modifications, post translation cleavages, relative charges, and other experimental factors. (novusbio.com)
  • Due to its high expression in the majority of solid tumors and the dependency of these tumors on the continuous and steady protein levels of HIF-1α for nutrient and oxygen supply, the transcription factor subunit has been recognized as a molecular target for cancer therapy. (omicsonline.org)
  • Zusätzlich bieten wir Ihnen Cytochrome C Oxidase Subunit IV Isoform 2 (Lung) Proteine (3) und viele weitere Produktgruppen zu diesem Protein an. (antikoerper-online.de)
  • Hypoxia which induces p53 protein accumulation, directly interacts with HIF1-alpha and reduces hypoxia-induced expression of HIF1-alpha by promoting MDM2-mediated ubiquitination and proteasomal degradation under hypoxic conditions. (fishersci.com)
  • A fusion protein including residues 530-825 of the mouse HIF-1 alpha protein. (fishersci.com)
  • In vitro, human neuroblastoma SH-SY5Y cells stably expressing wild-type amyloid-β protein precursor were exposed to either IH (8 cycles of 1% O 2 for 10 min followed by 21% O 2 for 20 min) or normoxia. (iospress.com)
  • HIF-1 α transcript and protein levels were found to be increased in xenon-exposed compared to air-exposed brains. (hindawi.com)
  • Sustained nuclear translocation of the protein, accounting for an increased activity of HIF-1 α , was also noted. (hindawi.com)
  • The time point for maximum knock-down rate for each protein can vary significantly, as it is depending on factors such as protein-stability, turn-over rate or cell proliferation rates. (eupheria.net)
  • Two approaches were used to monitor knock-down at protein level: 1. (eupheria.net)
  • HDAC2 mRNA and protein expression was reduced under hypoxic conditions (1% O2). (elsevier.com)
  • In a random series of 110 HCC patients, the mRNA of HIF-1alpha, inflammation related factors (COX-2, MMP7 and MMP9), angiogenesis related factors (VEGF and PDGFRA) and MYC in tumor tissue were detected by real-time RT-PCR and HIF-1alpha protein was assessed by immunohistochemistry. (beds.ac.uk)
  • The expression of both HIF-1alpha mRNA and protein in HCC were independent prognostic factors for overall survival (OS) ( P = 0.012 and P = 0.021, respectively) and disease-free survival (DFS) ( P = 0.004 and P = 0.007, respectively) as well. (beds.ac.uk)
  • The PHD2 enzyme interacts with a protein called hypoxia-inducible factor 2-alpha (HIF-2α). (nih.gov)
  • This protein is one part (subunit) of a larger HIF protein complex that plays a critical role in the body's ability to adapt to changing oxygen levels. (nih.gov)
  • This gene encodes the alpha subunit of transcription factor hypoxia-inducible factor-1 (HIF-1), which is a heterodimer composed of an alpha and a beta subunit. (nih.gov)
  • The alpha subunit forms a heterodimer with the beta subunit. (wikipedia.org)
  • HIF1 is a heterodimer composed of an alpha subunit and a beta subunit. (abnova.com)
  • The beta subunit has been identified as the aryl hydrocarbon receptor nuclear translocator (ARNT). (abnova.com)
  • Under hypoxic conditions, HIF mediates also a decrease in mRNA levels of the respiratory chain proteins, preparing the cell to produce ATP mainly from glycolysis and not from oxidative phosphorylation, thereby optimizing cell energetics and homeostasis for survival and function during hypoxia. (knowcancer.com)
  • In addition, SA suppresses the upstream signaling of HIF-1α, such as PI3K/Akt/mTOR, p42/p44 MAPK, and STAT3 signaling under hypoxic conditions. (nih.gov)
  • Salternamide A was identified for the first time as an inhibitor of HIF-1α accumulation under hypoxic conditions in cancer cells (Figure 6). (nih.gov)
  • It is stabilized only at O2 concentrations below 5% and upon stabilization under hypoxic conditions HIF-1 translocates to the nucleus. (abcam.com)
  • Hypoxia results in chemoresistance of human OS cells to doxorubicin.A, Dose-response curves for the 143B and MNNG/HOS (mHOS) cell lines treated with increasing concentrations of doxorubicin under normoxic and hypoxic conditions (72 hour, 0.5% O2). (nih.gov)
  • 94 Hypoxia Inducible Factor 1, alpha Subunit Inhibitor (HIF1AN) Anticorps de 16 fabricants sont disponibles sur www.anticorps-enligne.fr. (anticorps-enligne.fr)
  • Hypoxia inducible factor 1 alpha subunit inhibitor ) - білок, який кодується однойменним геном, розташованим у людей на короткому плечі 10-ї хромосоми. (wikipedia.org)
  • Contrary to other known FIH-1 inhibitors that have negative charges, Clioquinol and 8-hydroxyquinoline are neutral in charge and can provide a template for improved inhibitor design that can selectively inhibit FIH-1. (rcsb.org)
  • Taken together, SA was identified as a novel small molecule HIF-1α inhibitor from marine natural products and is potentially a leading candidate in the development of anticancer agents. (nih.gov)
  • Several studies mostly using mammalian cells or tissues discussed Hif-3α as a competitive inhibitor of Hif-1α and Hif-2α. (zfin.org)
  • Transcription factor HIF1α promotes proliferation, migration, and invasion of cholangiocarcinoma via long noncoding RNA H19/microRNA-612/Bcl-2 axis. (nih.gov)
  • The aim of this work was to evaluate the effects of semaphorin 3A (Sema3A) and hypoxia inducible factor 1 subunit alpha (HIF1α) co-overexpression on the survival and osteogenic differentiation of iPSC-MSCs. (bvsalud.org)
  • [email protected]#Modifying iPSC-MSCs with pro-osteogenic (Sema3A) and pro-survival (HIF1α) factors may represent a promising strategy to optimize tissue engineering-based strategy in bone repair. (bvsalud.org)
  • Only been successfully used with mouse HIF1 alpha. (abcam.com)
  • HIF is a heterodimer consisting of one of three subunits(HIF1-α, HIF2-α, or HIF3-α) bound to the aryl hydrocarbon receptor nuclear translocator(ARNT) that is also known as HIF1-β. (acris-antibodies.com)
  • Hypoxia-inducible factor-1 (HIF1) is a transcription factor found in mammalian cells cultured under reduced oxygen tension that plays an essential role in cellular and systemic homeostatic responses to hypoxia. (abnova.com)
  • HIF1-alpha regulates hypoxia-mediated apoptosis, cell proliferation and tumor angiogenesis. (fishersci.com)
  • Recent studies suggest that induction of NOX4 by HIF1-alpha contributes to maintain ROS levels after hypoxia and hypoxia-induced proliferation. (fishersci.com)
  • Here we investigate hypoxia-induced changes in the Wnt/β-catenin signaling pathway, a key signaling cascade involved in OS pathogenesis. (nih.gov)
  • Jun proto-oncogene (JUN), which was related to a cis-regulator lncRNA RP4-794H19.1, was enriched in cancers and involved in Tumor Necrosis Factor (TNF) signaling pathway, might play a key role in NPC. (jcancer.org)
  • Here we show that Hif-1α also binds to the promoter of the period 2 gene, indicating that multiple connections between the Hif signaling pathway and the circadian clock exist. (zfin.org)
  • Varicocele, also known as scrotal varices , is related to varicose veins and hypogonadotropism , and has symptoms including pain in scrotum An important gene associated with Varicocele is GNRH1 (Gonadotropin Releasing Hormone 1), and among its related pathways/superpathways are PI3K-Akt signaling pathway and Allograft rejection . (malacards.org)
  • Salternamide A Suppresses Hypoxia-Induced Accumulation of HIF-1α and Induces Apoptosis in Human Colorectal Cancer Cells. (nih.gov)
  • HIF-1 induces vascular endothelial growth factor and other angiogenic factors, thereby promoting angiogenesis. (springermedizin.de)
  • Tumor hypoxia induces nuclear paraspeckle formation through HIF-2α dependent transcriptional activation of NEAT1 leading to cancer cell survival. (ox.ac.uk)
  • Our data suggest that xenon induces the upregulation of HIF-1 α transcription and translation, which may contribute to xenon's neuroprotective preconditioning effect. (hindawi.com)
  • Here, we show that hypoxia induces corticosteroid-insensitive inflammation via reduced transcription of histone deacetylase-2 (HDAC2) in lung epithelial and macrophage cells. (elsevier.com)
  • HIF-1 thus plays an essential role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease. (nih.gov)
  • Hepatocyte growth factor (HGF) plays an important role in tumor growth and progression also by regulating invasive/metastatic phenotype and angiogenesis. (nih.gov)
  • When the eel is transferred from FW to SW, the intestinal wall decreases in thickness, and the anterior intestine became highly vascularized through angiogenesis within 1-2 days [ 8 ]. (biomedcentral.com)
  • Several studies indicate that, in the tumor microenvironment, TAMs acquire an M2-polarized phenotype and promote angiogenesis, metastasis, and suppression of adaptive immunity through the expression of cytokines, chemokines, growth factors, and matrix metalloproteases. (hindawi.com)
  • Alcohol promotes liver hypoxia, a trigger of angiogenesis. (cdc.gov)
  • We investigated the prognostic value of hypoxia-inducible factor-1 alpha (HIF-1alpha) in hepatocellular carcinoma (HCC), and its correlations with inflammation, angiogenesis and MYC oncogene. (beds.ac.uk)
  • EF24 overcomes sorafenib resistance through VHL-dependent HIF-1α degradation and NF-κB inactivation. (biomedsearch.com)
  • Under conditions where oxygen concentration is not limiting, HIF-α subunits are hydroxylated by prolyl-hydroxylases, targeting them for ubiquitin-mediated degradation by the von Hippel-Lindau tumor suppressor (VHL) ( 18 , 19 ). (asm.org)
  • In the presence of oxygen the α subunit is targeted for proteosomal degradation [ 11 , 12 ] ultimately inhibiting its dimerization to the β subunit, which is necessary for activation of the complex as a transcription factor. (omicsonline.org)
  • Accumulation of the α subunit is accomplished in extremely low oxygen levels or due to a variety of genetic abnormalities that avoid the degradation of the subunit [ 11 ]. (omicsonline.org)
  • Toll-Iike Receptor-3 Activation Enhances Malignant Traits in Human Breast Cancer Cells Through Hypoxia-inducible Factor-1alpha. (nih.gov)
  • Over-expression of hypoxia-inducible factor-1alpha increases the invasive potency of LNCaP cells in vitro. (nih.gov)
  • Selection and analysis of a mutant cell line defective in the hypoxia-inducible factor-1 alpha-subunit (HIF-1alpha). (ox.ac.uk)
  • Characterization of hif-1alpha-dependent and -independent hypoxia-inducible gene expression. (ox.ac.uk)
  • Comparison of hypoxia-inducible gene expression in wild type, HIF-1alpha-defective, and HIF-1alpha-complemented cells revealed two types of response. (ox.ac.uk)
  • These experiments show the utility of mutagenesis and selection of mutant cells in the analysis of mammalian transcriptional responses to hypoxia and demonstrate the operation of HIF-1alpha-dependent and HIF-1alpha-independent pathways of hypoxia-inducible gene expression in Chinese hamster ovary cells. (ox.ac.uk)
  • Induction of hypervascularity without leakage or inflammation in transgenic mice overexpressing hypoxia-inducible factor-1alpha. (abnova.com)
  • Genome-wide association of hypoxia-inducible factor (HIF)-1alpha and HIF-2alpha DNA binding with expression profiling of hypoxia-inducible transcripts. (ox.ac.uk)
  • Asparagine-803 in the C-terminal transactivation domain of human hypoxia-inducible factor (HIF)-1 alpha-subunit is hydroxylated by factor inhibiting HIF-1 (FIH-1) under normoxic conditions causing abrogation of the HIF-1alpha/p300 interaction. (ox.ac.uk)
  • The correlations between HIF-1alpha mRNA and the factors mentioned previously, the relationship between HIF-1alpha and clinicopathologic features, and the prognostic value were analyzed. (beds.ac.uk)
  • Functions as an oxygen sensor and, under normoxic conditions, the hydroxylation prevents interaction of HIF-1 with transcriptional coactivators including Cbp/p300-interacting transactivator. (uniprot.org)
  • The structure reveals the mechanism of specific recognition of p300 by HIF-1 alpha, and shows how HIF-1 alpha transactivation is regulated by asparagine hydroxylation. (rcsb.org)
  • Under normoxic conditions HIF-1α is continuously synthesized and degraded after hydroxylation by dioxygenases that utilize oxygen, Fe and α-ketoglutarate as substrates. (knowcancer.com)
  • Quinol family compounds such as 5-chloro-7-iodo-8-hydroxyquinoline (Clioquinol) have been shown to inhibit the hydroxylation activity of FIH-1. (rcsb.org)
  • HIF prolyl hydroxylases (PHDs) control HIF-1 accumulation by hydroxylation dependent on molecular oxygen. (gu.se)
  • Hypoxia-inducible factor asparaginyl hydroxylase (FIH-1) catalyses hydroxylation at the beta-carbon of asparagine-803. (ox.ac.uk)
  • The hypoxia-inducible transcription factor 1 alpha (HIF-1 alpha ) is the regulated member of the transcription factor heterodimer HIF-1. (novusbio.com)
  • Studies of asphyxia and hypoxia-ischemia, and also isoflurane toxicity and apoptosis, suggest that xenon may be a valuable preconditioning and neuroprotective anesthetic agent that does not exert neurotoxic effects in the fragile developing brain [ 1 , 7 , 8 , 16 - 18 ]. (hindawi.com)
  • HIF-α is a member of the basic helix-loop-helix (bHLH) superfamily, in which the HLH domain mediates subunit dimerization while the basic domain binds to DNA. (acris-antibodies.com)
  • HIF2α appears to be a more attractive target for the following reasons: its expression is more specific to tumor tissues, it mediates states of chronic hypoxia found in tumors, and specific inhibitors to target HIF2α exist 13 . (nature.com)
  • JMJD1A regulates the expression of adrenomedullin (ADM) and growth and differentiation factor 15 (GDF15) under hypoxia by decreasing promoter histone methylation. (asm.org)
  • Most clear cell renal cell carcinomas (ccRCC) are associated with loss of von Hippel-Lindau tumor suppressor (pVHL) function and deregulation of hypoxia pathways. (nih.gov)
  • Hypoxia-mediated sorafenib resistance can be overcome by EF24 through Von Hippel-Lindau tumor suppressor-dependent HIF-1α inhibition in hepatocellular carcinoma. (biomedsearch.com)
  • Cardiopulmonary function in two human disorders of the hypoxia-inducible factor (HIF) pathway: von Hippel-Lindau disease and HIF-2α gain-of-function mutation. (ox.ac.uk)
  • This antibody does not cross-react with ARNT or the related HIF-2-alpha. (abcam.com)
  • For mouse specific Hif-1-alpha rabbit monoclonal antibody, please see ab179483 (clone ID: EPR16897). (abcam.com)
  • Western Blot analysis of HIF3A expression in transfected 293T cell line ( H00064344-T01 ) by HIF3A MaxPab polyclonal antibody.Lane 1: HIF3A transfected lysate(40.04 KDa).Lane 2: Non-transfected lysate. (acris-antibodies.com)
  • Paraffin Embedded Human Kidney stained with HIF3A / HIF3 alpha Antibody Cat. (acris-antibodies.com)
  • Previous studies have shown that cetuximab, an EGF receptor-blocking monoclonal antibody, downregulates the alpha subunit of HIF-1 (HIF-1α) through the inhibition of EGF receptor downstream cell signaling and that downregulation of HIF-1α is required for cetuximab-induced antiproliferative effects. (aacrjournals.org)
  • This antibody detects upregulation of HIF-1 alpha in hypoxic samples. (fishersci.com)
  • Astrocytes infected with siHIF-1α showed abrogated hypoxic induction of vascular endothelial growth factor (VEGF) and lactate dehydrogenase (LDH) but normal EPO induction. (jneurosci.org)
  • ex vivo rat aortic ring assay, in vitro assessment of HUVEC proliferation and migration, and in vivo CAM assay, while we used the changes in the expression of HIF-1α and VEGF in breast cancer cells (MCF 7) as an indicative for the indirect antiangiogenic activity. (biomedcentral.com)
  • Hypoxia activates a complex gene expression program, mediated by hypoxia inducible factor 1 (HIF1alpha). (ox.ac.uk)
  • This review summarizes recent evidence from genetic and biological studies showing that hypoxia and hypoxia-related pathways play critical roles in the development and progress of renal cancer. (nih.gov)
  • The concentration of HGF was also significantly inversely correlated with severity of rash (p-value = 0.00124).High levels of HGF lead to increased signaling via its receptor MET, which can activate numerous pathways which are normally also activated by epidermal growth factor receptor. (bireme.br)
  • Proposed signaling pathways underlying the effects of SA on the suppression of HIF-1α and the induction of cell death in human colorectal cancer cells. (nih.gov)
  • The translational regulation of HIF-1α accumulation by SA was partly associated with the down-regulation of the axis of the PI3K/mTOR/STAT3 signaling pathways. (nih.gov)
  • The molecular links that connect cancer cells and TAMs are not completely known, but recent studies have demonstrated that NF- B, STAT-3, and HIF-1 signaling pathways play key roles in this crosstalk. (hindawi.com)
  • In this paper, we discuss the current knowledge about the role of TAMs in HCC development, highlighting the role of TAM-derived cytokines, chemokines, and growth factors in the initiation and progression of liver cancer and outlining the signaling pathways involved in the interplay between cancer cells and TAMs. (hindawi.com)
  • Recent studies have shown the importance of pH in cell death under hypoxia, thus mechanisms of pH regulation are likely to be vital pathways for survival. (ox.ac.uk)
  • JMJD2C decreases trimethylation of histone H3 at lysine 9, and enhances HIF-1 binding to hypoxia response elements, thereby activating transcription of BNIP3 , LDHA , PDK1 , and SLC2A1 , which encode proteins that are required for metabolic reprogramming, as well as LOXL2 and L1CAM , which encode proteins that are required for lung metastasis. (pnas.org)
  • We show that hypoxia results in increased expression and signaling activation of HIF proteins in human osteosarcoma cells. (nih.gov)
  • HCC microenvironment consists of (a) stromal cells, such as carcinoma-associated fibroblasts (CAFs), hepatic stellate cells (HSCs), endothelial cells and immune cells, (b) growth factors and inflammatory cytokines, and (c) extracellular matrix proteins [ 1 ]. (hindawi.com)
  • Hypoxia - inducible factors (HIFs) regulate adaptive responses to reduced O 2 availability in all metazoan species and play essential roles in embryonic development, postnatal physiology, and disease pathogenesis ( 2 ⇓ ⇓ ⇓ ⇓ - 7 ). (pnas.org)
  • The investigators will investigate the effect of hypobaria and hypoxia on physiological responses such as: oxygen saturation, heart rate, cerebral blood flow, cerebral oxygenation, brain's. (bioportfolio.com)
  • Identifying early gene expression responses to hypoxia ( i.e. , low dissolved oxygen) as a tool to assess the degree of exposure to this stressor is crucial for salmonids, because they are increasingly exposed to hypoxic stress due to anthropogenic habitat change, e.g. , global warming, excessive nutrient loading, and persistent algal blooms. (g3journal.org)
  • HIF-1α is a master regulator of essential adaptive responses to hypoxia, whose expression and transcriptional activity increasing exponentially with decreases in levels of cellular oxygen. (beds.ac.uk)
  • Hypoxia-inducible factor (HIF)-1α is an important transcriptional regulator of cellular responses to hypoxia, oxidants and inflammation, and is overexpressed in the lungs of COPD patients. (edu.au)
  • The massive transcriptional reorganization mediated by hypoxia and HIFs suggests that changes in histone modification would create epigenetic reinforcement of this phenotype ( 20 ). (asm.org)
  • HIF-1α function has been shown to influence and be influenced by histone deacetylases ( 22 , 33 ), yet comparatively little is known regarding HIF-dependent dynamics of histone methylation ( 8 , 21 ). (asm.org)
  • Effective assessment of low times MET amplification in pleural effusion after epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) acquired resistance: Cases report. (bireme.br)
  • RATIONALE: The mechanism of the first-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) acquired resistance included T790M mutation, cellular-mesenchymal to epithelial transition factor (MET) or EGFR amplification, PIK3CA mutation, and transformation to small cell lung cancer. (bireme.br)
  • Epidermal growth factor receptor overexpression in human cancer can be effectively targeted by drugs acting as specific inhibitors of the receptor, like erlotinib, gefitinib, cetuximab and panitumumab. (bireme.br)
  • We studied molecules involved in epidermal growth factor receptor signaling which are quantifiable in plasma, with the aim of identifying biomarkers for the severity of rash. (bireme.br)
  • Increased HGF/MET signaling might compensate the inhibitory effect of epidermal growth factor receptor inhibitors in skin as well as tumor cells, leading to less severe skin rash and decreased efficacy of the anti-tumor therapy, rendering the plasma concentration of HGF a candidate for predictive biomarkers. (bireme.br)
  • Moreover, tyrosine 10 (Y10) phosphorylation of LDHA is common in diverse human cancers, and phosphorylated LDHA Y10 levels directly correlate with the activities of several oncogenic tyrosine kinases, including fibroblast growth factor receptor 1 (FGFR1), Janus kinase 2 (JAK2), breakpoint cluster region/ABL proto-oncogene 1 (BCR/ABL) and fms related tyrosine kinase 3- internal tandem duplication (FLT3-ITD) [ 24 ]. (ijbs.com)
  • Recent evidence shows that increased HIF-1α expression can upregulate the platelet-activating factor receptor (PAFR) on the airway epithelial surface that is increased in smokers and particularly COPD patients. (edu.au)
  • MYPT1, the targeting subunit of smooth-muscle myosin phosphatase, is a substrate for the asparaginyl hydroxylase factor inhibiting hypoxia-inducible factor (FIH). (wikipedia.org)
  • Hypoxia inducible factor (HIFs) signaling contributes to malignant cell behavior in glioblastoma (GBM). (nature.com)
  • Despite a well-described link between hypoxia and malignancy, targeting HIFs in oncology has not led to therapeutic advances in the clinic. (nature.com)
  • In addition, using an in vitro model of oxygen-glucose deprivation (OGD), we studied the role of HIF-1α and HIF-2α in the generation of paracrine protective signals by astrocytes that modulate the survival of neurons exposed to OGD. (jneurosci.org)
  • Hypoxia is an element intrinsic to most solid-tumor microenvironments, including that of OS, and is associated with resistance to therapy, poor survival, and a malignant phenotype. (nih.gov)
  • Long-term oxygen therapy improves survival in patients with severe hypoxia. (bioportfolio.com)
  • Factors Associated with Survival of Patients With Severe Acute-On-Chronic Liver Failure Before and After Liver Transplantation. (amedeo.com)
  • Hypoxia inducible carbonic anhydrase IX, marker of tumour hypoxia, survival pathway and therapy target. (ox.ac.uk)
  • The transcription factor HIF-1 plays an important role in cellular response to systemic oxygen levels in mammals. (wikipedia.org)
  • These sequences generally contain one or more binding sites for a heterodimeric DNA binding complex termed hypoxia-inducible factor-1 (HIF-1). (ox.ac.uk)
  • Generally, CN is made up of two heterodimeric subunits, CNA and CNB. (peerj.com)
  • BACKGROUND: Hypertension (HTN) may lead to left ventricular hypertrophy and vascular dysfunction, which are independent factors for adverse cardiovascular outcomes. (biomedsearch.com)
  • Cellular hypoxia occurs when the demands of growth and metabolism of a tissue surpass the vascular oxygen supply. (asm.org)
  • WB: COS-7 cells treated with 1% oxygen for 4 hours to induce hypoxia. (abcam.com)
  • Promoter analysis confirmed the presence of hypoxia response elements in the promoter region of the PNUTS gene, which respond to hypoxia and forced expression of hypoxia-inducible factor 1 alpha. (thebiogrid.org)
  • Carbonic anhydrase IX: A highly specific promoter for hypoxia mediated gene therapy. (ox.ac.uk)
  • Uribe DJ, Shin YJ, Lau E, Ebbinghaus SW, Sun D (2013) Heterogeneous Nuclear Ribonucleoprotein K Binds to the Cytosine-Rich Sequence of the Hypoxia Inducible Factor 1 Alpha Proximal Promoter that forms a Stable i-motif at Neutral pH. (omicsonline.org)
  • The proximal promoter of the hypoxia inducible factor 1 alpha (HIF-1α) gene contains a poly-purine/poly-pyrimidine (pPu/pPy) tract, which has been shown to affect 90% of its transcriptional control. (omicsonline.org)
  • In present study, we demonstrated that the cytosine-rich (C-rich) sequence within the pPu/pPy tract of the HIF-1α promoter is able to form two major intramolecular i-motif structures with 3:3:3 or 3:4:2 folding patterns near physiological pH using circular dichroism, bromine footprinting and site-directed mutational analysis. (omicsonline.org)
  • Taken together, our results demonstrate that the i-motif structures that form within the C-rich sequence of the HIF-1α promoter can form under physiological conditions and that hnRNP K can bind to this C-rich sequence. (omicsonline.org)
  • Medicine (Baltimore) ;97(1):e9021, 2018 Jan. (bireme.br)
  • Association between HIF-1α gene polymorphisms and lung cancer: A meta-analysis. (nih.gov)
  • 1% within the cases, are filtered out at an early stage of data analysis, as these variants are assumed to be common polymorphisms. (aacrjournals.org)
  • Recently, a large number of epidemiological studies have investigated the relationship between HIF-1α C1772T/G1790A polymorphisms and cancer susceptibility. (cdc.gov)
  • Pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for the relationship between HIF-1α C1772T/G1790A polymorphisms and cancer susceptibility were calculated using fixed- and random-effects models when appropriate. (cdc.gov)
  • Functional HIF-1α 1744C/T, VEGFA 2578C/A, and KDR 1416A/T single-nucleotide polymorphisms were studied in 125 ALD patients and 88 heavy drinkers without liver disease (NLD). (cdc.gov)
  • Genetic polymorphisms in proangiogenic factors did not associate with the risk of ALD in heavy drinkers. (cdc.gov)
  • In well-oxygenated cells, HIF-α subunits are hydroxylated on proline residues by prolyl hydroxylases (PHDs) in the presence of reaction substrates (O 2 and α-ketoglutarate) and cofactors (iron and ascorbate) ( 13 ). (pnas.org)
  • Therefore we recommend western blots using nuclear extracts and running Hypoxia treated samples as positive control ( ab180880 ). (abcam.com)
  • Moreover, Tumor-Necrosis-Factor-alpha (TNF- α )-induced Nuclear Factor kappa B (NF- κ B) activation plays a key role in hepatocarcinogenesis [ 7 , 8 ]. (hindawi.com)
  • In the present study, we demonstrate the potential role of PP1 nuclear targeting subunit (PNUTS) in regulating the phosphorylation and apoptotic activities of p53. (thebiogrid.org)
  • 31P nuclear magnetic resonance study of steady-state adenosine 5'-triphosphate levels during graded hypoxia in the isolated perfused rat kidney. (ox.ac.uk)
  • HIF-1α has been shown to be up-regulated and stabilized in LPS-treated macrophages and monocytes under normoxic conditions. (knowcancer.com)
  • Under normoxic conditions HIF-1 alpha has a short half-life. (abcam.com)
  • In this context a detailed analysis of the mRNA concentrations of hif-1 α, hif-2 α, and hif-3 α also revealed a circadian expression pattern for hif-3 α mRNA under normoxic conditions in zebrafish larvae. (zfin.org)
  • Further, qPCR of the 30 candidate hypoxia biomarkers was applied to an additional 322 Chinook salmon exposed to hypoxic and normoxic conditions to reveal the top biomarkers to define hypoxic stress. (g3journal.org)
  • These were accompanied by increased myocardial expression of hypoxia-inducible factor (HIF)-1α, inflammation, and microvascular remodeling, including increased density of epicardial microvessels (20-200 µm), as well as cardiac diastolic dysfunction, all of which improved by reversal of HTN. (biomedsearch.com)
  • Recent published reports have linked inflammation and endotoxin stimulation to HIF-1α activation. (knowcancer.com)
  • Inflammation is an early and transient event in MS and remyelination occurs afterwards ( 1 ). (frontiersin.org)
  • Here, we review the evidence for the roles of local tissue hypoxia-induced inflammation, HIF-1α and PAFR in facilitating bacterial infections in COPD. (edu.au)
  • Hypoxia contributes significantly to the pathophysiology of major categories of human disease, including myocardial and cerebral ischemia, cancer, pulmonary hypertension, congenital heart disease and chronic obstructive pulmonary disease. (fishersci.com)
  • Experimental studies into forms of anesthetic-induced preconditioning (APC), including hypoxia and sublethal ischemia, have indicated that preconditioning occurs in two waves (early and delayed) and with two potencies (short/immediate and long/deferred) [ 11 ]. (hindawi.com)
  • HIF-1α and CTGF expression of both testes in group 3 were studied by real-time reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. (elsevier.com)
  • Therefore, SA is a leading candidate for the development of anticancer agents, and these mechanisms will be a key therapeutic target for pharmacologic and therapeutic intervention in HIF-1α-driven tumor growth and cell death. (nih.gov)
  • The high metabolic rate required for tumor growth often leads to hypoxia in poorly-perfused regions. (ox.ac.uk)
  • CNA acts as catalytic subunit of phosphatase while the basic function of CNB is to regulate the activity of CNA ( Rusnak & Mertz, 2000 ). (peerj.com)
  • In this study, we investigated the differential contribution of hypoxia inducible factor (HIF) isoforms to the regulation of hypoxic EPO expression in cultured astrocytes. (jneurosci.org)
  • In zebrafish, as in most vertebrates, three different isoforms of the hypoxia-inducible transcription factor, Hif-1α, Hif-2α, and Hif-3α, have been identified. (zfin.org)
  • have described a simple method of differentiating human ES cells (hESCs) into MSCs by switching hES cells from ES medium to defined medium, which consisted of DMEM-low glucose, 10% FBS and 1% Penicillin/Streptomycin, followed by trypsinization-based passaging 15 . (nature.com)
  • Maintenance of oxygen homeostasis underlies many developmental and physiological processes, and disturbances of oxygen homeostasis play key roles in the pathogenesis of many human diseases, including cancer, diabetes, and ischemic cardiovascular disease ( 1 ). (pnas.org)
  • Simple Western lane view shows lysates of A549 human lung carcinoma cell line untreated (-) or treated (+) with Hypoxia (1% O2), loaded at 0.2 mg/mL. (novusbio.com)
  • Western blot shows lysates of HeLa human cervical epithelial carcinoma parental cell line and HIF-1 alpha knockout HeLa cell line (KO) untreated (-) or treated (+) with 1 mM DFO overnight. (novusbio.com)
  • Detects human, mouse, and rat HIF-1 alpha. (novusbio.com)
  • In the present study, we demonstrate that SA efficiently inhibits the hypoxia-induced accumulation of HIF-1α in a time- and concentration-dependent manner in various human cancer cells. (nih.gov)
  • Recombinant fragment corresponding to Human HIF-1 alpha aa 530-826 (C terminal). (abcam.com)
  • within Human HIF-1 alpha aa 600-700 (C terminal). (abcam.com)
  • Down regulation of Wnt signaling mitigates hypoxia-induced chemoresistance in human osteosarcoma cells. (nih.gov)
  • Hypoxia has been shown to promote resistance to cytotoxic drugs in other human OS cell lines [12]. (nih.gov)
  • Hepatocellular carcinoma (HCC) is one of the most aggressive human cancers and the third leading cause of death worldwide [ 1 ]. (hindawi.com)
  • HIF-1α overexpression has been shown to be a predictive factor of recurrence and distant metastasis in the majority of common human solid tumors and is positively associated with increased patient mortality [ 2 , 13 ]. (omicsonline.org)
  • Human and nonhuman primate studies of maternal obesity demonstrate that risk factors for pediatric obesity and NAFLD begin in utero. (jci.org)
  • However, some patients despite this oxygen, experience episodes of low oxygen levels (intermittent hypoxia) espe. (bioportfolio.com)
  • However, it is poorly assessed whether chronic intermittent hypoxia (CIH), which is a characteristic of OSA, affects the pathophysiology of AD. (iospress.com)
  • We aimed to investigate the direct effect of intermittent hypoxia (IH) in pathophysiology of AD in vivo and in vitro. (iospress.com)
  • Analysis of these cells revealed several clones with transacting defects in HRE activation, and in one the defect was identified as a failure to express the alpha-subunit of HIF-1. (ox.ac.uk)
  • CONCLUSION: Hypoxia induced by sustained sorafenib treatment confers sorafenib resistance to HCC through HIF-1α and NF-κB activation. (biomedsearch.com)
  • Immune cell activation mandates an increase in energy requirements, thus a reduced production of ATP due to impaired mitochondrial function may be a factor in modulating the immune response in sepsis. (knowcancer.com)
  • Two distinct activation sites: AF-1 and AF-2 enable transcriptional activation (Heldring et al. (springeropen.com)
  • Hypoxia is defined as any level of DO that is low enough to negatively impact the behavior and/or physiology of an organism. (g3journal.org)
  • This gene encodes the alpha subunit of HIF-1. (abnova.com)
  • Natural products as sources of new fungicides (IV): Synthesis and biological evaluation of isobutyrophenone analogs as potential inhibitors of class-II fructose-1,6-bisphosphate aldolase. (bireme.br)
  • Hypoxia and hyperoxia, referring to states of biological tissues in which oxygen supply is in-sufficient and too much, respectively, are often pathological conditions. (bioportfolio.com)
  • When the brain detects a drop in oxygen levels in the blood (hypoxia) there is a compensatory increase in blood flow. (bioportfolio.com)
  • However, when oxygen levels are lower than normal (hypoxia), the PHD2 enzyme becomes less active. (nih.gov)