• Activation of PKM2 using two well-characterized small molecules, DASA-58 and TEPP-46, inhibited LPS-induced Hif-1α and IL-1β, as well as the expression of a range of other Hif-1α-dependent genes. (nih.gov)
  • Hypoxia Inducible Factors Modulate Mitochondrial Oxygen Consumption and Transcriptional Regulation of Nuclear-Encoded Electron Transport Chain Genes. (nih.gov)
  • HIF-1α is a ubiquitous, constitutively synthesized transcription factor responsible for upregulating the expression of genes involved in the cellular response to hypoxia. (wikipedia.org)
  • With low levels of oxygen, HIF-2α binds to HIF-1β creating a transcription complex that stimulates hypoxia-inducible gene transcription, including genes for erythropoiesis, angiogenesis and cellular proliferation which can promote cancer cell growth. (nih.gov)
  • Patients with VHL disease have a defective protein that does not bind HIF-2α, leaving it free to bind HIF-1β and increase transcriptions of genes of angiogenesis and tumor cell growth. (nih.gov)
  • The hypoxia-inducible factor 1 (HIF-1) has been identified as a master regulator for the expression of genes involved in the hypoxia response, such as genes coding for glucose transporters, glycolytic enzymes and vascular endothelial growth factor (VEGF). (mmu.ac.uk)
  • HIF-1 achieves this by binding to hypoxia response elements in the promoter regions of these genes, whereby the increase of HIF-1 in hypoxia is the consequence of a reduced degradation of its dominant subunit HIF-1[alpha]. (mmu.ac.uk)
  • Genetic mutations might also directly affect the equilibrium of these metabolic factors, through the effects of oncogenes and tumor-suppressor genes (such as HRAS , ERBB2 and TP53 ). (medscape.com)
  • Conversely, when oxygen levels are insufficient (hypoxia), prolyl hydroxylation and subsequent HIF-α destruction are avoided, allowing HIF-α to bind to HIF-β at the nuclear hypoxia response elements and, therefore, activate expression in numerous genes (Figure 1). (medscape.com)
  • In specific cases, the cells are engineered for knock out of one or more genes, such as Signaling Threshold Regulating Transmembrane Adaptor 1 (SIT1), Bone Marrow Stromal Cell Antigen 2 (BST2), and/or programmed cell death protein 1 (PD-1). (justia.com)
  • In particular embodiments, the genes that are knocked out or knocked down are Signaling Threshold Regulating Transmembrane Adaptor 1 (SIT1), Bone Marrow Stromal Cell Antigen 2 (BST2), and Programmed cell death protein 1 (PD-1). (justia.com)
  • Thus, in specific embodiments, the expression of SIT1, BST2, and PD-1 is altered through genetic modification that results in improved T cell resistance or TIL resistance to immunosuppression compared to T cells or TIL, respectively, that do not have deliberate modification of expression of these genes. (justia.com)
  • The mixture altered genes associated with pathways such as "genotoxicity" and "nuclear factor erythroid 2-related factor 2 (Nrf2). (nih.gov)
  • However, increased glycolysis was not underpinned by up-regulation of metabolic genes encoding enzymes participating in glycolysis. (oaepublish.com)
  • The oxygen-regulated control system responsible for the induction of erythropoietin (Epo) by hypoxia is present in most (if not all) cells and operates on other genes, including those involved in energy metabolism. (ox.ac.uk)
  • The hypoxia-inducible factor (HIF) pathway regulates a cascade of genes allowing survival in low-oxygen conditions. (medscape.com)
  • 10. Genetic analysis of the role of the asparaginyl hydroxylase factor inhibiting hypoxia-inducible factor (FIH) in regulating hypoxia-inducible factor (HIF) transcriptional target genes [corrected]. (nih.gov)
  • The transcription factor Gli is prevented from entering the nucleus through interactions with cytoplasmic proteins like Suppressor of fused homolog (Sufu) and transcriptional activation of Shh target genes is repressed [ 1 ]. (biomedcentral.com)
  • Genes up-regulated in comparison of dendritic cells (DC) stimulated with LPS (TLR4 agonist) at 1 h versus DC cells stimulated with poly(I:C) (TLR3 agonist) at 1 h. (gsea-msigdb.org)
  • Vitamin D's antiprostate cancer activities may be involved in the actions through the pathways mediated by vitamin D metabolites, vitamin D metabolizing enzymes, vitamin D receptor (VDR), and VDR-regulated genes. (vitamindwiki.com)
  • We hypothesize that testicular HIF-1 activates the expression of antiapoptotic target genes to protect Leydig cells from apoptosis. (biomedcentral.com)
  • In silico analysis of testis genes containing a consensus hypoxia response element (HRE, 5'-RCGTG-3') identified myeloid cell leukemia-1 ( Mcl - 1 ) as a potential HIF-1 target gene. (biomedcentral.com)
  • Hypoxia-inducible factor-1 (HIF-1), often described as a "master" regulator of hypoxic responses in mammalian cells, is a well-characterized transcription factor known to activate over 100 different hypoxia-sensitive genes involved in a range of metabolic processes including anti- and proapoptotic responses to ischemia and hypoxia [ 1 , 2 ]. (biomedcentral.com)
  • Homologs of these genes also exist in mammals, and they have been implicated in the response of a cell to hypoxia or more generally as stress-induced genes having either pro- or anti-apoptotic functions. (sdbonline.org)
  • To gain a more comprehensive understanding of the role of HIF1 in mitochondrial homeostasis, we studied the link between hypoxia, HIF1 transactivation, and electron transport chain (ETC) function. (nih.gov)
  • In contrast to earlier assumptions it is now established that permanent or long-term exposure to severe environmental hypoxia decreases the mitochondrial content of muscle fibres. (mmu.ac.uk)
  • The SDHD protein helps anchor the SDH enzyme in the mitochondrial membrane. (nih.gov)
  • Consistent with the concept of mitohormesis, GlcN promotes increased formation of mitochondrial reactive oxygen species (ROS) culminating in increased expression of the nematodal amino acid-transporter 1 ( aat-1 ) gene. (anti-agingfirewalls.com)
  • Ameliorating mitochondrial ROS formation or impairment of aat-1 -expression abolishes GlcN-mediated life span extension in an NRF2/SKN-1-dependent fashion. (anti-agingfirewalls.com)
  • It is caused by the progressive, uncontrolled action of degradative ENZYMES, leading to MITOCHONDRIAL SWELLING, nuclear flocculation, and cell lysis. (lookformedical.com)
  • Hypoxia-inducible factor prolyl hydroxylase 2 (HIF-PH2), or prolyl hydroxylase domain-containing protein 2 (PHD2), is an enzyme encoded by the EGLN1 gene. (wikipedia.org)
  • The PHD2 enzyme interacts with a protein called hypoxia-inducible factor 2-alpha (HIF-2α). (medlineplus.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. (medlineplus.gov)
  • Some EGLN1 gene mutations change single protein building blocks (amino acids) in the PHD2 enzyme, while others lead to the production of an abnormally short version of the enzyme. (medlineplus.gov)
  • When oxygen levels are sufficient to meet cellular demand (normoxia), HIF-α subunits are subjected to oxygen-dependent prolyl hydroxylation, which promotes an interaction with von Hippel-Lindau (VHL) protein, an E3 ubiquitin ligase. (medscape.com)
  • Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits thereby driving them into their inactive GDP-bound form. (nih.gov)
  • Moreover, augmented 11βHSD1(-/-) adipose tissue angiogenesis is associated with enhanced peroxisome proliferator-activated receptor γ (PPARγ)-inducible expression of the potent angiogenic factors VEGF-A, apelin, and angiopoietin-like protein 4. (ox.ac.uk)
  • To link metastatic propensity to a hypoxia-induced proteotype, we compared the protein profiles of two isogenic canine OS cell lines, POS (low metastatic) and HMPOS (highly metastatic), under normoxia and hypoxia. (nature.com)
  • Cell migration and glucose uptake assays combined with protein function inhibitor studies provided further support that hypoxia-driven adaption of pathways associated with glycolytic metabolism, collagen biosynthesis and remodeling, redox regulation and immunomodulatory proteins typify a proteotype associated with an aggressive cancer cell phenotype. (nature.com)
  • Therefore, the identification of hypoxia-inducible protein targets responsible for cancer progression, malignant transformation and metastasis is needed for deepening our understanding of OS biology. (nature.com)
  • 15. Factor inhibiting HIF-1 (FIH-1) modulates protein interactions of apoptosis-stimulating p53 binding protein 2 (ASPP2). (nih.gov)
  • The electrons are transferred through the SDH subunits, including the SDHD protein, to the oxidative phosphorylation pathway. (nih.gov)
  • In particular, succinate stabilizes a protein called hypoxia-inducible factor (HIF) by preventing a reaction that would allow HIF to be broken down. (nih.gov)
  • Most of the inherited SDHD gene mutations associated with hereditary paraganglioma-pheochromocytoma type 1 change single protein building blocks (amino acids) in the SDHD protein sequence or result in a shortened protein. (nih.gov)
  • As in GIST (described above), the reduction of SDH enzyme activity stabilizes the HIF protein, causing it to build up in cells. (nih.gov)
  • MCL-1 protein expression was evaluated by immunoblot analysis and immunohistochemistry. (biomedcentral.com)
  • MCL-1 protein was determined to be abundant in both normoxic and ischemic testes and expressed in Leydig cells. (biomedcentral.com)
  • In normoxia, HIF alpha subunits are marked for the ubiquitin-proteasome degradation pathway through hydroxylation of proline-564 and proline-402 by PHD2. (wikipedia.org)
  • The signalling pathway terms "PI3K-Akt", "transforming growth factor-β receptor", "ErbB", and "HIF-1" from the functional annotation analysis were studied. (nature.com)
  • These results indicate that human PAECs express and secrete BDNF in response to hypoxia via a HIF-1-regulated pathway. (elsevierpure.com)
  • Here we show that adipose tissues of 11βHSD1(-/-) mice exhibit attenuated hypoxia, induction of hypoxia-inducible factor (HIF-1α) activation of the TGF-β/Smad3/α-smooth muscle actin (α-SMA) signaling pathway, and fibrogenesis despite similar fat accretion with diet-induced obesity. (ox.ac.uk)
  • 2. Ankyrin Repeat Proteins of Orf Virus Influence the Cellular Hypoxia Response Pathway. (nih.gov)
  • Na,K-ATPase β 1 -subunit is a target of the Shh signaling pathway and loss of β 1 -subunit expression may contribute to tumor development and progression not only in carcinoma but also in medulloblastoma, a tumor of neuronal origin. (biomedcentral.com)
  • Based on these considerations, we developed the antiangiogenic hypoxic cell radiosensitizers, TX-1877, TX-1898 and the hypoxic cytotoxin TX-402 that inhibits the HIF-1α pathway We will also discuss our research involved with the development of other drugs to exploit tumor hypoxia, including a hypoxia-targeting boron carrier for boron neutron capture therapy (BNCT) and a p53 inhibiting radiosensitizer. (go.jp)
  • Several lines of evidence indicate that Scylla and Charybdis feed into the Inr pathway downstream of PKB: (1) Scylla antagonizes PKB/PDK1-induced overgrowth in the eye, but in vitro kinase assays demonstrate that Scylla and Charybdis do not reduce PKB kinase activity, nor does the loss of Scylla enhance PKB kinase activity. (sdbonline.org)
  • A PHD2 knockdown showed increased levels of HIF-1α under normoxia, and an increase in HIF-1α nuclear accumulation and HIF-dependent transcription. (wikipedia.org)
  • Separately, in human PAECs exposed for 24h to normoxia vs. hypoxia (1-3% O 2 ), ELISA of extracellular media showed increased BDNF levels. (elsevierpure.com)
  • In normoxia, interaction between hypoxia-inducible factor alpha subunits and von Hippel-Lindau complex is promoted by oxygen-dependent prolyl hydroxylation of hypoxia-inducible factor alpha subunits. (medscape.com)
  • Activation of cAMP by forskolin had no effect on the level of LDH mRNA in normoxia, but produced a magnified response to hypoxia that was dependent upon the integrity of the CRE, indicating an interaction between inducible factors binding the HIF-1 and CRE sites. (ox.ac.uk)
  • z Hypoxia − z Normoxia ) to quantitatively evaluate the proteome shifts exhibited by OS cells in response to hypoxia. (nature.com)
  • Our data suggest that HIF1α regulates transcription of cytochrome c oxidase (CcO) heart/muscle isoform 7a1 (Cox7a1) under hypoxia, where it is induced 1.5-2.5-fold, whereas Cox4i2 hypoxic induction was HIF1α-independent. (nih.gov)
  • We propose that adaptation to hypoxic stress of CcO as the main cellular oxygen consumer is mediated by induction of hypoxia-sensitive tissue-specific isoforms. (nih.gov)
  • Diffusion-weighted imaging has the highest prognostic value and pseudo-normalizes following 1 week of hypoxic-ischemic injury. (bvsalud.org)
  • Hypoxic regulation of lactate dehydrogenase A. Interaction between hypoxia-inducible factor 1 and cAMP response elements. (ox.ac.uk)
  • The most important of these, although not capable of driving hypoxic induction in isolation, had the consensus of a hypoxia-inducible factor 1 (HIF-1) site, and cross-competed for the binding of HIF-1 with functionally active Epo and phosphoglycerate kinase-1 sequences. (ox.ac.uk)
  • The second domain was positioned close to the HIF-1 site, in an analogous position to one of the critical regions in the Epo 3' hypoxic enhancer. (ox.ac.uk)
  • Solid tumors are characterized by intratumoral hypoxia, and hypoxic cells are associated with the transformation to aggressive phenotype and metastasis. (nature.com)
  • 1. Ferritin heavy chain controls the HIF-driven hypoxic response by activating the asparaginyl hydroxylase FIH. (nih.gov)
  • In this study, we identify a role for the hypoxic inducible factor (HIF) signalling axis to inhibit SARS-CoV-2 infection, epithelial damage and respiratory symptoms in the Syrian hamster model. (bvsalud.org)
  • Progress in the development of hypoxia-targeting drugs will be discussed, including antiangiogenic hypoxic cell radiosensitizers and hypoxic cytotoxins, hypoxia targeting boron carriers and p53-inhibiting bifunctional radiosensitizers. (go.jp)
  • Measurements of the physiological oxygen tension in the testis indicate that testicular pO 2 levels are likely low, bordering on hypoxia [ 16 - 18 ] and it has been suggested that other factors such as reactive oxygen species render the testis hypoxic even under presumptive normoxic conditions. (biomedcentral.com)
  • scylla is transcriptionally induced as a target of Drosopohila HIF-1 (the Tango-Similar dimer) and that scylla and charybdis are up-regulated under hypoxic conditions like their mammalian homolog RTP801/REDD1. (sdbonline.org)
  • The decrease in oxygen tension stimulates further angiogenesis through various signaling pathways, via production of numerous transcriptional factors. (medscape.com)
  • 16. Tuning the Transcriptional Response to Hypoxia by Inhibiting Hypoxia-inducible Factor (HIF) Prolyl and Asparaginyl Hydroxylases. (nih.gov)
  • 18. FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor. (nih.gov)
  • Oxygen levels in the microenvironment define the transcriptional landscape, however the influence of hypoxia on virus replication and disease in animal models is not well understood. (bvsalud.org)
  • Belzutifan is a small molecule inhibitor of hypoxia-inducible factor 2 alpha used to treat solid tumors in patients with von Hippel-Lindau disease. (nih.gov)
  • Belzutifan (bel zue' ti fan) is an oral small molecule inhibitor of hypoxia-inducible factor 2 alpha (HIF-2α) which is elevated in tumors of patients with von Hippel-Lindau (VHL) disease. (nih.gov)
  • 3. Inhibitor of nuclear factor-kappaB alpha derepresses hypoxia-inducible factor-1 during moderate hypoxia by sequestering factor inhibiting hypoxia-inducible factor from hypoxia-inducible factor 1alpha. (nih.gov)
  • cyclin dependent kinase inhibitor 1. (gsea-msigdb.org)
  • Hypoxia inducible factor-1 (HIF1) is a stress-responsive nuclear transcription factor that is activated with a decrease in oxygen availability. (nih.gov)
  • Hypoxia and BDNF also induced expression of hypoxia inducible factor 1 alpha (HIF-1α), a subunit of the transcription factor HIF-1, and pharmacological inhibition of HIF-1 diminished hypoxia effects on BDNF expression and secretion, and NO production. (elsevierpure.com)
  • The transcription factor HIF consists of two subunits, α and β. (medscape.com)
  • The AHR is a ligand-dependent transcription factor and key regulator in xenobiotic metabolism and immunity. (frontiersin.org)
  • In this context, the AHR, a ligand-activated transcription factor and key regulator in xenobiotic metabolism and immunity, seems to be a promising molecular target. (frontiersin.org)
  • Previously, we demonstrated that the hypoxia-inducible factor-1 (HIF-1) transcription factor, a key regulator of physiological responses to hypoxia, is abundant in Leydig cells in normoxic and ischemic testes. (biomedcentral.com)
  • Key influencing factors during this transition included the interaction between the extracellular matrix (ECM) and matrix metalloproteinase (MMPs) along with nuclear components such as, histone HIST1H1T (H1.6). (nature.com)
  • In hypoxia, hypoxia-inducible factor alpha binds to hypoxia-inducible factor beta at the nuclear hypoxia response elements. (medscape.com)
  • Hypoxia is a condition commonly observed in the core of solid tumors. (mdpi.com)
  • Furthermore, discovery of the hypoxia inducible factor 1α (HIF-1α) has led to a rapidly increasing understanding of the molecular mechanisms involved in tumor hypoxia. (go.jp)
  • This in turn has led to the current extensive interest in the signal molecules related to tumor hypoxia as potential molecular targets for cancer therapeutics. (go.jp)
  • In this paper we give an overview of recent advances in hypoxia research, including cancer treatments that target tumor hypoxia. (go.jp)
  • The differences that are especially significant but not well known is 1) metabolic changes in the regulation of glucose homeostasis and lipid metabolism 2) regulation of vascular function and structural effects on the heart and arteries 3) regulation of skeletal muscle mass and fat tissue 4) morphological and functional effects on discrete areas of the brain. (stanford.edu)
  • HIF is a regulator of oxygen homeostasis that has an oxygen-sensitive subunit (2α) and a constitutively expressed subunit (1β). (nih.gov)
  • We first demonstrated in cell culture models that the hypoxia-inducible factor 1α (HIF-1α), a master regulator of oxygen homeostasis, induces genetic alterations by inhibiting DNA repair. (utah.edu)
  • Na,K-ATPase is a ubiquitous enzyme that maintains intracellular ion homeostasis and functions as a signaling scaffold and a cell adhesion molecule. (biomedcentral.com)
  • These gene products may include proteins such as glycolytic enzymes and angiogenic growth factors. (wikipedia.org)
  • Mediation of the physiological and pathological stimulation that causes a change in cellular phenotype is enacted by a variety of proangiogenic factors, which include secreted proteins, transcription factors, cytokines, oncogenes, trace elements, proteases, enzymes and low-molecular-weight mediators. (medscape.com)
  • Hypothesis-driven parallel reaction monitoring was used to validate the differential proteins observed in the shotgun data and to monitor proteins of which we expected to exhibit hypoxia responsiveness, but which were absent in the label-free shotgun data. (nature.com)
  • Evaluation of the sensitivity scores for the proteome shifts observed and principal component analysis of the hypoxia-responsive proteins indicated that both cell types acquire a proteome that supports a Warburg phenotype with enhanced cell migration and proliferation characteristics. (nature.com)
  • Therefore the two related proteins, Scylla and Charybdis, are negative modulators of Inr/TOR signaling in response to different external stress situations including hypoxia and starvation. (sdbonline.org)
  • This gene is a hypoxia-inducible factor-1 dependent, hypoxia-induced gene which is involved in the induction of endothelial apoptosis. (nih.gov)
  • For instance, infection of mice with herpes simplex 1 virus followed by induction of M2 macrophages through CSF-1 DNA was associated with reduced virus replication in the eye, reduced latency and reduced levels of CD4, CD8, IFN-γ and PD-1 transcripts in the trigeminal ganglion [ 2 ]. (biomedcentral.com)
  • Although models of NEC are not uniform, the majority involve induction with a combination of bacteria or their products with hypoxia and/or hypothermia or ischemia. (biomedcentral.com)
  • This notion is supported by the observations that impairment of either skn-1 or aat-1 abrogates the effects of GlcN on life span and disruption of SKN-1 prohibits the induction of aat-1 expression in nematodes. (anti-agingfirewalls.com)
  • Binds to G(i)-alpha and G(o)-alpha, but not to G(s)-alpha (By similarity). (nih.gov)
  • The ELISA and EMSA assays demonstrated that testicular HIF-1 from normoxic and ischemic testes binds DNA equally strongly, suggesting physiological roles for HIF-1 in the normoxic testis, unlike most tissues in which HIF-1 is degraded under normoxic conditions and is only activated by hypoxia. (biomedcentral.com)
  • Overall, this study provides an insight into regulatory factors and pathways during preantral ovarian folliculogenesis in domestic cat. (nature.com)
  • How exactly ROS interfere with HIF-1[alpha] as well as MAP kinase and other signalling pathways is debated. (mmu.ac.uk)
  • Succinate, the compound on which the SDH enzyme acts, is an oxygen sensor in the cell and can help turn on specific pathways that stimulate cells to grow in a low-oxygen environment (hypoxia). (nih.gov)
  • In response to mild hyperthermic stress, the Heat Shock Response (HSR) and the endoplasmic reticulum (ER) stress response pathways are activated and preserve the integrity of important signaling networks to sustain cell survival under stressful conditions [ 1 - 3 ]. (oncotarget.com)
  • In some subjects with inherited pheochromocytoma/paraganglioma (PPG) syndromes, hypoxia-inducible factor 1 alpha (HIF1α) stabilization/activation could lead to an increase in angiotensin converting enzymes (ACE). (nih.gov)
  • It is also known as Egl nine homolog 1. (wikipedia.org)
  • scylla/charybdis , like their mammalian homolog, are induced by hypoxia, and scylla is a direct target of Drosopohila HIF-1. (sdbonline.org)
  • Non-melanoma skin cancers, in particular basal cell carcinoma and SCC, are among the most frequent malignancies in humans ( 1 - 3 ). (frontiersin.org)
  • To explore the impact of the cell phenotype on the hypoxia-responsive proteome we chose two isogenic canine OS cell lines with different phenotypes: POS (primary origin) displaying a low metastatic phenotype and HMPOS (metastatic origin) exemplifying a highly metastatic phenotype 18 . (nature.com)
  • Changes in Na,K-ATPase function and subunit expression have been reported in several cancers and loss of the β 1 -subunit has been associated with a poorly differentiated phenotype in carcinoma but its role in medulloblastoma progression is not known. (biomedcentral.com)
  • Mechanistically, the life span-extending phenotype is rather linked to an activation of SKN-1/NRF-2-dependent transcription, as the latter not only promotes longevity of C. elegans independently of GlcN 16 , 32 , 38 , 39 , 40 , 41 , 42 but also following GlcN exposure (this study). (anti-agingfirewalls.com)
  • The hypoxia-inducible factors (HIF) act as hypoxia sensors that orchestrate a coordinated response increasing the pro-survival and pro-invasive phenotype of cancer cells, and determine a broad metabolic rewiring. (mdpi.com)
  • The reason why belzutifan might cause serum enzyme elevations is not known, but it is metabolized in the liver by the cytochrome P450 system (predominantly CYP 2C19 and to a lesser extend 3A4) and liver injury may be the result of production of a toxic or immunogenic metabolic intermediate. (nih.gov)
  • This might occur as a result of metabolic stresses such as hypoxia, acidosis, inflammation or immune-cell activation. (medscape.com)
  • Increased angiogenesis protects against adipose hypoxia and fibrosis in metabolic disease-resistant 11β-hydroxysteroid dehydrogenase type 1 (HSD1)-deficient mice. (ox.ac.uk)
  • Mice lacking the intracellular glucocorticoid-amplifying enzyme 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1(-/-)) have "healthier" adipose tissue distribution and resist metabolic disease with diet-induced obesity. (ox.ac.uk)
  • the modulation of both fatty acid synthesis and oxidation are hallmarks of the metabolic rewiring induced by hypoxia. (mdpi.com)
  • Therefore, the investigators will follow these patients for a year to study how the heart, blood vessels, brain, and risk factors for cardiovascular disease affected by altered sex hormone patterns and studying what happens in the muscles and fat in both the short and long term with respect to particular gene expression and epigenetic changes and link it to metabolic changes and body composition. (stanford.edu)
  • 5. Inhibition of the Oxygen-Sensing Asparaginyl Hydroxylase Factor Inhibiting Hypoxia-Inducible Factor: A Potential Hypoxia Response Modulating Strategy. (nih.gov)
  • [9] Proline hydroxylation is also a vital component of hypoxia response via hypoxia inducible factors . (wikipedia.org)
  • ATF4 and CHOP are well characterized stress response factors proximal to eIF2α. (oncotarget.com)
  • The Golgi apparatus is a highly reactive organelle that exhibits functional and morphological perturbations in response to molecular-level and contextual factors. (molcells.org)
  • The tumor microenvironment is now recognized as a major factor that influences not only the response to conventional anti-cancer therapies but also helps define the potential for malignant progression and metastasis. (go.jp)
  • The anti-tumor activities of hypoxia response are considered to be cytostatic (tumor dormancy-inducing) effects in contrast to cytotoxic DNA damaging effects. (go.jp)
  • The testicular HIF-1 DNA-binding capacity was analyzed in vitro using a quantitative enzyme-linked immunosorbent assay (ELISA) and electrophoretic mobility shift assays (EMSA). (biomedcentral.com)
  • HIF-1α steady state accumulation was dependent on the amount of PHD silencing effected by siRNA in HeLa cells and a variety of other human cell lines. (wikipedia.org)
  • Its members are X factor (HEMIN) independent and variably dependent on V factor (NAD). (nih.gov)
  • They are OXYGEN-dependent enzymes that play an important role in mediating cellular adaptive responses to HYPOXIA . (nih.gov)
  • Other hydroxylating agents include flavins, alpha-ketoglutarate-dependent hydroxylases , and some diiron hydroxylases. (wikipedia.org)
  • We show that LPS-induced PKM2 enters into a complex with Hif-1α, which can directly bind to the IL-1β promoter, an event that is inhibited by activation of PKM2. (nih.gov)
  • overexpression of Bmi1 reduced β 1 -subunit promoter activity. (biomedcentral.com)
  • Chromatin immunoprecipitation (ChIP) analysis using a HIF-1 antibody revealed sequences enriched for the Mcl - 1 promoter. (biomedcentral.com)
  • The EGLN1 gene, often known as PHD2 , provides instructions for making an enzyme called prolyl hydroxylase domain 2 (PHD2). (medlineplus.gov)
  • This genetic change alters the interaction between the PHD2 enzyme and HIF-2α, which leads to the production of excess red blood cells. (medlineplus.gov)
  • In specific embodiments, the disclosure concerns adoptive cell therapy cancer treatment in which tumor-1 infiltrating lymphocytes and/or engineered T cells are modified to increase their efficacy as a cancer treatment. (justia.com)
  • In particular embodiments, all three of SIT1, BST2, and PD-1 are knocked out or knocked down, although in alternative embodiments only one or two of SIT1, BST2, and PD-1 are knocked out or knocked down in the cells. (justia.com)
  • Embodiments of the disclosure allow for improved T cell resistance to immunosuppression compared to T cells with un-altered expression of SIT1, BST2, and PD-1, including to overcome immunosuppression in the tumor microenvironment. (justia.com)
  • Na,K-ATPase β 1 -subunit was knocked down in DAOY cells to test its role in medulloblastoma cell proliferation and tumorigenicity. (biomedcentral.com)
  • Na,K-ATPase β 1 -subunit levels increased with differentiation in normal CGP cells. (biomedcentral.com)
  • In human medulloblastoma cells, low β 1 -subunit levels were associated with increased cell proliferation and in vivo tumorigenesis. (biomedcentral.com)
  • Psoriasis development involves genetic and environmental factors triggering inflammatory cascades involving keratinocytes, neutrophils, dendritic cells, and T-helper (Th) cells. (emjreviews.com)
  • In contrast, seropositive donor cultures seeded at the higher cell concentrations developed foci of proliferating EBNA-positive cells within the first 1--2 weeks but thereafter regressed completely and subcultures made after 4 weeks never gave rise to cell lines. (nih.gov)
  • In a pattern identical to that of HIF-1 expression, the steady-state levels of MCL-1 were not significantly affected by I or I/R and MCL-1 co-localized with HIF-1α in Leydig cells. (biomedcentral.com)
  • The results demonstrated that, unlike what is observed in most tissues, HIF-1 displays DNA-binding activity in both normoxic and ischemic testes, and Mcl - 1 may be a key target gene of testicular HIF-1 with potential roles in the antiapoptotic protection of Leydig cells. (biomedcentral.com)
  • HIF-1 can have antiapoptotic or apoptotic effects on cells depending on the extent and duration of the oxygen debt [ 11 ]. (biomedcentral.com)
  • We hypothesize that HIF-1 plays important roles in mediating antiapoptotic responses in the testis and may protect Leydig cells from apoptosis. (biomedcentral.com)
  • To examine the significance of the sulfation of L-selectin ligands, our group has generated gene-targeted mice deficient in both N -acetylglucosamine-6- O -sulfotransferase (GlcNAc6ST)-1 and GlcNAc6ST-2. (go.jp)
  • The mutant mice show approximately 75% less lymphocyte homing to the peripheral lymph nodes than normal, indicating that GlcNAc6ST-1 and GlcNAc6ST-2 play a major role in the biosynthesis of L-selectin ligand in HEV. (go.jp)
  • To understand the organization of cis-acting sequences that are responsible for oxygen-regulated gene expression, we have studied the 5' flanking region of the mouse gene encoding the hypoxically inducible enzyme lactate dehydrogenase A (LDH). (ox.ac.uk)
  • The transmembrane receptor Patched 1 (Ptch1) inhibits the activity of the Smoothened (Smo) receptor. (biomedcentral.com)
  • Importantly, both exposomal factors unleash their carcinogenic potential, at least to some extent, by activating the aryl hydrocarbon receptor (AHR). (frontiersin.org)
  • 6. MYPT1, the targeting subunit of smooth-muscle myosin phosphatase, is a substrate for the asparaginyl hydroxylase factor inhibiting hypoxia-inducible factor (FIH). (nih.gov)
  • Perinatal hypoxia-ischemia (HI) is a leading cause of morbidity and mortality among newborns. (bvsalud.org)
  • RTP801 was described as a hypoxia/HIF-1-inducible factor with a role in apoptosis (Shoshani, 2002). (sdbonline.org)
  • Previous studies from my lab and others have indicated a critical role for hypoxia (low oxygen tension) in malignant progression. (utah.edu)
  • [ 7 ] Table 1 lists the different stimulators and inhibitors of angiogenesis involved in urologic cancers. (medscape.com)
  • A recent study found a second peptide binding site on PHD2 although peptide binding to this alternative site did not seem to affect the catalytic activity of the enzyme. (wikipedia.org)
  • Many such catalysts are biomimetic, i.e. they are inspired by or intended to mimic enzymes such as cytochrome P450. (wikipedia.org)
  • 11. Kinetic Investigations of the Role of Factor Inhibiting Hypoxia-inducible Factor (FIH) as an Oxygen Sensor. (nih.gov)
  • The majority of breast cancer-related deaths are not caused by the primary tumor itself, but are due to the results of metastasis to vital organs [ 1 ] . (oaepublish.com)
  • PHD2 is a 46-kDa enzyme that consists of an N-terminal domain homologous to MYND zinc finger domains, and a C-terminal domain homologous to the 2-oxoglutarate dioxygenases. (wikipedia.org)
  • PHD2 is the primary regulator of HIF-1α steady state levels in the cell. (wikipedia.org)
  • However, although it would seem that PHD2 downregulates HIF-1α and thus also tumorigenesis, there have been suggestions of paradoxical roles of PHD2 in tumor proliferation. (wikipedia.org)
  • When enough oxygen is available, the PHD2 enzyme is highly active to stimulate the breakdown of HIF-2α. (medlineplus.gov)
  • However, when oxygen levels are lower than normal (hypoxia), the PHD2 enzyme becomes less active. (medlineplus.gov)
  • The mutation, written as His374Arg or H374R, replaces the amino acid histidine with the amino acid arginine at position 374 in the PHD2 enzyme. (medlineplus.gov)