• 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)
  • Its interactions with HIF-1α rely on a mobile loop region that helps to enclose the hydroxylation site and helps to stabilize binding of both iron and 2-oxyglutarate. (wikipedia.org)
  • Two alpha-ketoglutarate dependent non-heme iron dioxygenases are responsible for the regulation of HIF-1 through hydroxylation of residues on the HIF-1a subunit. (umass.edu)
  • Examples of a novel series of phenanthrolinones are shown to be potent competitive inhibitors of avian prolyl 4-hydroxylase, and of collagen hydroxylation, in embryonic chick tendon cells and human foreskin fibroblasts in vitro and in the oestradiol-stimulated rat uterus in vivo. (embl.de)
  • Two compounds, Compound 1 (1,4-dihydrophenanthrolin-4-one-3-carboxylic acid) and Compound 5 [8-(N-butyl-N-ethylcarbamoyl)-1,4-dihydrophenathrolin-4-one-3-carboxylic acid], with comparable potencies in vivo, were chosen to investigate the effect of the inhibition of the hydroxylation of newly synthesized uterine collagen on the turnover of this protein in vivo. (embl.de)
  • Taken with the present results, this suggests that the potential use of inhibitors of prolyl 4-hydroxylase to control excessive collagen deposition in pathological fibrosis may be limited by the need to maintain continuous inhibition of collagen hydroxylation so as to facilitate intracellular degradation of the accumulated protein. (embl.de)
  • Collagen prolyl 4-hydroxylase (P4H) expression and collagen hydroxylation in cancer cells are necessary for breast cancer progression. (uky.edu)
  • The hypoxic response in animals is mediated by hydroxylation of proline residues in the alpha-subunit of hypoxia inducible factor (HIF). (ox.ac.uk)
  • Hydroxylation is catalysed by prolyl-4-hydroxylases (PHD isozymes in humans) which are iron(II) and 2-oxoglutarate dependent oxygenases. (ox.ac.uk)
  • At normal oxygen levels, the alpha subunit of HIF is targeted for degration by prolyl hydroxylation. (antikoerper-online.de)
  • In the normal cell with active VHL protein, HIF alpha is regulated by hydroxylation in the presence of oxygen. (standardofcare.com)
  • Aspartyl beta-hydroxylase: In vitro hydroxylation of a synthetic peptide based on the structure of the first growth factor-like domain of human factor IX. (bjbms.org)
  • Hydroxylation of aspartic acid in domains homologous to the epidermal growth factor precursor is catalyzed by a 2-oxoglutarate-dependent dioxygenase. (bjbms.org)
  • Masson N., Willam C., Maxwell P., Pugh C., Ratcliffe P. Independent function of two destruction domains in hypoxia-inducible factor-alpha chains activated by prolyl hydroxylation. (ulsu.ru)
  • The regulation of HIF-1α occurs at the posttranslational level involving modifications of hydroxylation, acetylation and phosphorylation ( 3 - 7 ). (spandidos-publications.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)
  • METHODS AND RESULTS: Stabilization of myocardial HIF-1 was achieved by pharmacological inhibition of prolyl hydroxylase (PHD) domain-containing enzyme using GSK360A or using cardiac-specific ablation of von Hippel-Lindau protein (VHL(fl/fl)) in mice. (ox.ac.uk)
  • Co-expression of Ov-phy-1 with the O. volvulus homologue of protein disulfide isomerase in a baculovirus system resulted in the production of enzymatically active O. volvulus prolyl 4-hydroxylase. (embl.de)
  • This control is propagated through the alpha-subunit of prolyl 4-hydroxylase where protein levels were previously shown to rise fivefold with increasing cell density. (embl.de)
  • B and T lymphocyte attenuator (BTLA) is an inhibitory receptor, similar to cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed death 1 (PD1), that negatively regulates the immune response. (cnrs.fr)
  • Following modification HIF- alpha chains are captured by a ubiquitin ligase E3 complex containing the von Hippel-Lindau (VHL) tumour suppressor protein. (ox.ac.uk)
  • protein_coding" "Cz02g32120.t1","No alias","Chromochloris zofingiensis","B-block binding subunit of TFIIIC [Interproscan]. (ntu.edu.sg)
  • protein_coding" "Cz03g26100.t1","No alias","Chromochloris zofingiensis","Pre-mRNA polyadenylation factor Fip1 domain [Interproscan]. (ntu.edu.sg)
  • Estrogen modulation of HIF-1 and subsequent effects on endothelial cells is dependent on the Akt/PI3K pathway and protein synthesis as validated by the use of the inhibitors wortmannin and cycloheximide which abrogated estrogen's effects respectively. (biomedcentral.com)
  • Hypoxia maintains HIFα protein expression through inhibition of prolyl hydroxylases and IL-1 is suggested to effect subunit expression at the level of transcription and in a similarly post-translational fashion [ 26 ]. (biomedcentral.com)
  • We show that ionizing radiation specifically enhances the motility and invasiveness of human GSCs through the stabilization and nuclear accumulation of the hypoxia-inducible factor 1α (HIF1α), which in turn transcriptionally activates the Junction-mediating and regulatory protein (JMY). (nature.com)
  • We show that radiation-induced migration/invasion occurs through the stabilization and nuclear accumulation of the transcription factor hypoxia-inducible factor 1 alpha (HIF1α), which drives the transcription of Junction-mediating and regulatory protein (JMY) 27 that stimulates GSC migration through its actin nucleation-promoting activity. (nature.com)
  • Aspartate β-hydroxylase (ASPH) is a type II transmembrane protein and the member of α-ketoglutarate-dependent dioxygenase family, found to be overexpressed in different cancer types, including PC. (bjbms.org)
  • Semenza G., Wang G. A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation. (ulsu.ru)
  • Bishop T., Ratcliffe P. Signaling hypoxia by hypoxia-inducible factor protein hydroxylases: a historical overview and future perspectives. (ulsu.ru)
  • The presence of Remodelin could suppress the elevated level of HIF-1α protein and its nuclear translocation induced by either treatment of cobalt chloride (CoCl2) or hypoxia in dose or time-dependent way. (cd4inhibitors.com)
  • pVHL is best known as the substrate-binding subunit of an E3 ubiquitin ligase, which binds the transcription elongation factors C and B (elongin C/B) forms the VCB complex, then interacts with Cullin-2 (CUL2) and the RING finger protein RBX1 forming the VCB-CR complex(3). (biomedcentral.com)
  • Serum insulin-like growth factor (IGF)-I and IGF-binding protein-3 concentrations and prostate cancer risk: results from the European Prospective Investigation into Cancer and Nutrition. (mdc-berlin.de)
  • This compound markedly decreased the hypoxia-induced accumulation of HIF-1α protein dose-dependently, whereas it did not affect the expressions of HIF-1β and topoisomerase-I (topo‑I). Furthermore, celastrol prevented hypoxia-induced expression of HIF-1 target genes for vascular endothelial growth factor (VEGF) and erythropoietin (EPO). (spandidos-publications.com)
  • Further analysis revealed that celastrol inhibited HIF-1α protein synthesis, without affecting the expression level of HIF-1α mRNA or degradation of HIF-1α protein. (spandidos-publications.com)
  • Markedly, we found that suppression of HIF-1α accumulation by celastrol correlated with strong dephosphorylation of mammalian target of rapamycin (mTOR) and its effectors, ribosomal protein S6 kinase (p70S6K) and eukaryotic initiation factor 4E (eIF4E) and extracellular signal-regulated kinase (ERK), pathways known to regulate HIF-1α expression at the translational level. (spandidos-publications.com)
  • A third vertebrate P4H type is an ER transmembrane protein that can act on HIF-alpha but not on collagens. (indexindex.com)
  • 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)
  • The control of oxygen delivery to cells in the body is the result of a small group of primary oxygen sensors, one of the most important of which is the hypoxia-inducible transcription factor-1 (HIF-1). (umass.edu)
  • In studies during the early 1990's, Gregg Semenza identified, and then in 1995 purified and cloned, a transcription factor that regulates these oxygen-dependent responses. (nobelprize.org)
  • Through the combined work of these three laureates it was thus demonstrated that the response by gene expression to changes in oxygen is directly coupled to oxygen levels in the animal cell, allowing immediate cellular responses to occur to oxygenation through the action of the HIF transcription factor. (nobelprize.org)
  • Once formed, the complex translocates to the nucleus where it acts as a transcription factor by binding to the estrogen response elements (EREs) at the promoters of estrogen responsive genes[ 9 , 10 ]. (biomedcentral.com)
  • HIF-1 is also a heterodimeric transcription factor, consisting of the oxygen dependent alpha subunit and the constitutively expressed beta subunit. (biomedcentral.com)
  • The hypoxia-inducible transcription factor 1 alpha (HIF-1 alpha) is the regulated member of the transcription factor heterodimer HIF-1. (bio-techne.com)
  • The most studied target of VHL is hypoxia inducible factor 1a (HIF1a), a transcription factor that induces the expression of a number of angiogenesis related factors. (standardofcare.com)
  • HIF transcription factor distribution in kidney cancer is of major importance in determining the outcome of the patients. (standardofcare.com)
  • In contrast, cancer cells shift their metabolism toward lactate production even in the presence of oxygen [ 4 ], partly through genetic modifications that stabilize the transcription factor Hypoxia Inducible Factor (HIF) involved in the adaptation of the cells to hypoxia, under nonhypoxic conditions as well as generating an adaptive response to the hypoxic microenvironment (Figure 1 ). (hindawi.com)
  • Another P4H family, the HIF-P4Hs, hydroxylates specific prolines in the alpha subunit of the hypoxia-inducible transcription factor (HIF), a master regulator of hypoxia-inducible genes, and controls its stability in an oxygen-dependent manner. (indexindex.com)
  • VHL within the VHL:ElonginB:ElonginC:CUL2:RBX1 Complex binds HIF-alpha subunits that have hydroxylated proline residues (Cockman et al. (reactome.org)
  • During hypoxia, the proline residues are not hydroxylated and pVHL cannot bind. (standardofcare.com)
  • Under normoxic conditions, prolyl hydroxylases (PHDs) hydroxylate the cite-specific proline residues of HIF-1α in a reaction that uses O 2 as a substrate. (spandidos-publications.com)
  • Preconditioning of Cardiosphere-Derived Cells With Hypoxia or Prolyl-4-Hydroxylase Inhibitors Increases Stemness and Decreases Reliance on Oxidative Metabolism. (ox.ac.uk)
  • Hypoxic preconditioning was mimicked by treatment with two types of hypoxia-inducible factor (HIF) prolyl-4-hydroxylase inhibitors (PHDIs): dimethyloxaloylglycine (DMOG) and 2-(1-chloro-4-hydroxyisoquinoline-3-carboxamido) acetic acid (BIC). (ox.ac.uk)
  • It was hypothesized that there would be a difference in inhibition of FIH-1 from the other HIF-1 regulating enzyme, the prolyl hydroxylase domain-2 (PHD2), when testing a series of ten small molecule inhibitors. (umass.edu)
  • Adult and embryonic Brugia malayi are shown to be susceptible to inhibitors of vertebrate prolyl 4-hydroxylase, with exposed parasites exhibiting pathologies consistent with a disruption in cuticle biosynthesis. (embl.de)
  • In vitro production of enzymatically active O. volvulus prolyl 4-hydroxylase should facilitate identification of specific inhibitors of the parasite enzyme. (embl.de)
  • Agents such as tyrosine kinase, MAPK, PI3K, or hypoxia inducible factor inhibitors, alone or in combination, may represent novel therapeutic strategies that could be evaluated in prospective clinical trials. (thieme-connect.com)
  • In a search for HIF-1 inhibitors, we identified celastrol as an inhibitor of HIF-1 activation from Tripterygium wilfordii. (spandidos-publications.com)
  • Treatment of HL-1 cardiac cells with GSK360A stabilized HIF-1, increased the expression of HIF-1 target genes pyruvate dehydrogenase kinase-1 (PDK1) and hexokinase II (HKII), and reprogrammed cell metabolism to aerobic glycolysis, thereby resulting in the production of less mitochondrial oxidative stress during IRI, and less MPTP opening, effects which were shown to be dependent on HKII. (ox.ac.uk)
  • One of these enzymes, known as the factor inhibiting HIF-1 (FIH-1) is responsible for hydroxylating residue Asn 803 on HIF-1a, preventing the transcription of hypoxia related genes controlled by HIF-1. (umass.edu)
  • The gene encoding the Ov-phy-1 open reading frame contained 11 introns, similar in structure to the gene encoding human prolyl 4-hydroxylase isoform I. Genomic Southern blot, EST and genomic PCR studies demonstrated that the O. volvulus genome contained between three and eight genes closely related to Ov-phy-1. (embl.de)
  • Both canonical HIF-1α and HIF-2α target genes were overexpressed in the SDH/VHL cluster, suggesting that a global HIF deregulation accounts for this common profile. (nih.gov)
  • Nevertheless, when we compared VHL tumors with SDHB cases, which often exhibit a malignant behavior, we found that HIF-1α target genes showed a predominant activation in the VHL PCCs. (nih.gov)
  • An important mediator in this process is the hypoxia-inducible factor (HIF) complex, which is activated in hypoxic cells and increases transcription of a broad range of genes including angiogenic growth factors such as VEGF. (ox.ac.uk)
  • Hypoxia-inducible factor (HIF) modulates transcriptional control of several genes involved in vascular growth and cellular metabolism. (ox.ac.uk)
  • HIF-1 binds to hypoxia-response elements (HREs) in the promoters of many genes involved in adapting to an environment of insufficient oxygen or hypoxia. (bio-techne.com)
  • This heterodimer of HIF activates genes that encode for proteins such as vascular endothelial growth factor (VEGF) and erythropoietin, proteins that are both involved in angiogenesis. (standardofcare.com)
  • The elevated HIF-1α accumulates and makes a translocation to the nucleus, regulating the expression of target genes in the nucleus, which regulate a variety of cellular processes to promote survival. (cd4inhibitors.com)
  • 5′-GACGTG-3′) on the promoter region in various target genes ( 1 , 2 ). (spandidos-publications.com)
  • this association is primarily based on the HIF-1-mediated regulation of genes that play pivotal roles in the central features of cancer pathogenesis such as angiogenesis, invasion, metastasis and anti-apoptosis. (spandidos-publications.com)
  • These gene products may include proteins such as glycolytic enzymes and angiogenic growth factors. (wikipedia.org)
  • The levels of HIF-α isoforms are regulated in an oxygen-dependent manner by the activity of the HIF prolyl-hydroxylases (PHD or EGLN enzymes), which are Fe(II) and 2-oxoglutarate (2OG) dependent oxygenases. (ox.ac.uk)
  • The derived amino acid sequence of Ov-phy-1 encoded a peptide that was most similar to the two Caenorhabditis elegans prolyl 4-hydroxylase homologues and to the isoform II enzymes of vertebrates. (embl.de)
  • Regulation is through the modification of specific prolines in HIF- alpha chains which are hydroxylated by a recently identified family of enzymes which require molecular oxygen and 2-oxoglutarate as cosubstrates, and iron as a cofactor. (ox.ac.uk)
  • The HIF prolyl hydroxylases (PHD enzymes) act as oxygen sensors regulating HIF, and hence angiogenesis. (ox.ac.uk)
  • The process of the degradation of the hypoxia-inducible factors (HIFs) that mainly regulate oxygen and iron dependent activity of enzymes require DHL tumor suppressor. (standardofcare.com)
  • Canonical regulation of HIF abundance is governed after transcription and translation in part due to the action of oxygen sensitive enzymes, the hif-α prolyl hydroxylases. (biomedcentral.com)
  • By stimulating the expression of glucose transporters and glycolytic enzymes, HIF-1 promotes glycolysis to generate more pyruvate [ 5 ]. (hindawi.com)
  • 3 2 Under physiological hypoxia, low oxygen levels lead to reduced activity of succinate dehydrogenase (SDH), which metabolizes succinate, and other oxygen-dependent enzymes in the electron transport chain, causing succinate accumulation. (haematologica.org)
  • In humans, PHD2 is one of the three isoforms of hypoxia-inducible factor-proline dioxygenase, which is also known as HIF prolyl-hydroxylase. (wikipedia.org)
  • PHD2 is a α-ketoglutarate/2-oxoglutarate-dependent hydroxylase, a superfamily non-haem iron-containing proteins. (wikipedia.org)
  • Interestingly, estrogen is also capable of contributing to breast cancer progression by a novel role, via modulation of proteins involved in hypoxia signaling, namely hypoxia inducible factor 1 (HIF-1). (biomedcentral.com)
  • 5 4 Succinate functions as a competitive inhibitor for prolyl hydroxylase domain (PHD) proteins that are central to degradation of hypoxia-inducible factor (HIF)-1α subunit. (haematologica.org)
  • In vivo studies further confirmed the inhibitory effect of celastrol on the expression of HIF-1α proteins, leading to a decreased growth of Hep3B cells in a xenograft tumor model. (spandidos-publications.com)
  • HIF-1 reduces ischaemia-reperfusion injury in the heart by targeting the mitochondrial permeability transition pore. (ox.ac.uk)
  • We investigated whether HIF-1α stabilization protects the heart against acute IRI by preventing the opening of the mitochondrial permeability transition pore (MPTP) and the potential mechanisms involved. (ox.ac.uk)
  • These findings were further confirmed when HIF-1 stabilization in the rat and murine heart resulted in smaller myocardial infarct sizes (both in vivo and ex vivo), decreased mitochondrial oxidative stress, and inhibited MPTP opening following IRI, effects which were also found to be dependent on HKII. (ox.ac.uk)
  • CONCLUSIONS: We have demonstrated that acute HIF-1α stabilization using either a pharmacological or genetic approach protected the heart against acute IRI by promoting aerobic glycolysis, decreasing mitochondrial oxidative stress, activating HKII, and inhibiting MPTP opening. (ox.ac.uk)
  • Furthermore, HIF-1 actively limits the mitochondrial consumption of pyruvate at two levels: (i) through the enzyme PDK (PDH-kinase), which in turn inhibits PDH activity preventing the conversion of pyruvate into acetyl CoA, and thereby limiting mitochondrial metabolism of pyruvate [ 6 ] and (ii) through the direct activation of LDH [ 7 , 8 ]. (hindawi.com)
  • A HIF1alpha regulatory loop links hypoxia and mitochondrial signals in pheochromocytomas. (thieme-connect.com)
  • Bell E., Chandel N. Mitochondrial Oxygen sensing: regulation of Hypoxia-inducible factor by mitochondrial generated reactive oxygen species. (ulsu.ru)
  • 2001). VHL constitutively shuttles between the cytosol and nucleoplasm (Lewis and Roberts 2003) and though the VHL:HIF-alpha complex is predominantly nuclear, binding and degradation can occur in both the cytosol and the nucleus (Berra et al. (reactome.org)
  • ER degradation enhancing alpha-mannosida. (gsea-msigdb.org)
  • The modified HIF-1α interacts with Von Hippel-Lindau (VHL), which is part of the E3 ubiquitin ligase complex targeting HIF-1α for 26S proteasomal degradation. (spandidos-publications.com)
  • Using the murine mammary cell line TG1-1 we observed estrogen (E 2 ) lead to an up regulation of hypoxia inducible factor-1 (HIF-1), an effect abrogated by the anti-estrogen Fulvestrant and the HIF-1 inhibitor YC-1 (3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole) suggesting the interchangeability of hypoxia and estrogen mediated effects. (biomedcentral.com)
  • antizyme inhibitor 1 [Source:HGN. (gsea-msigdb.org)
  • Our data suggested that celastrol is an effective inhibitor of HIF-1 and provide new perspectives into the mechanism of its anticancer activity. (spandidos-publications.com)
  • PHD2 is the primary regulator of HIF-1α steady state levels in the cell. (wikipedia.org)
  • The asparaginyl hydroxylase factor inhibiting HIF-1alpha is an essential regulator of metabolism. (cnrs.fr)
  • Our data provide evidence that estrogen signaling mediates the tumor vasculogenic process required for breast cancer progression and involves a key regulator of the hypoxia signaling pathway. (biomedcentral.com)
  • niban apoptosis regulator 1 [Source:HGNC. (gsea-msigdb.org)
  • Inhibition of prolyl 4-hydroxylase in vitro and in vivo by members of a novel series of phenanthrolinones. (embl.de)
  • Prolyl hydroxylase inhibition results in primary cilia elongation also associated with accumulation of HIF-2α in the ciliary base and axoneme. (biomedcentral.com)
  • This is associated with increased HIF-2α expression and inhibited response to prolyl hydroxylase inhibition. (biomedcentral.com)
  • The enzyme has a high affinity for iron(II) and 2-oxoglutarate (also known as α-ketoglutarate), and forms a long-lived complex with these factors. (wikipedia.org)
  • The enzyme responsible for collagen maturation is prolyl 4-hydroxylase, making this enzyme a central activity in cuticle biosynthesis and a potentially important chemotherapeutic target. (embl.de)
  • A new Nature Communications study led by UK Markey Cancer Center researchers suggests that an enzyme known as Prolyl 4-hydroxylase subunit alpha-1 (P4HA1) is a potential therapeutic target for treating triple-negative breast cancer. (uky.edu)
  • 1,4-alpha-glucan branching enzyme 1 [Sou. (gsea-msigdb.org)
  • Description: This is Double-antibody Sandwich Enzyme-linked immunosorbent assay for detection of Horse Transforming Growth Factor Beta 1 (TGFb1) in serum, platelet-poor plasma, tissue homogenates, cell lysates, cell culture supernates and other biological fluids. (stemcellcharter.org)
  • Description: Enzyme-linked immunosorbent assay based on the Double-antibody Sandwich method for detection of Horse Transforming Growth Factor Beta 1 (TGFb1) in samples from serum, platelet-poor plasma, tissue homogenates, cell lysates, cell culture supernates and other biological fluids with no significant corss-reactivity with analogues from other species. (stemcellcharter.org)
  • HIF activity can be enhanced by suppression of prolyl and asparaginyl hydroxylase activity by dimethyloxalylglycine (DMOG). (ox.ac.uk)
  • A feedback regulation mechanism that involves the displacement of HIF-1α by hydroxylated HIF-1α when 2-oxoglutarate is limiting was also proposed. (wikipedia.org)
  • Hypoxic tissue environments occur in vascular and pulmonary diseases as well as cancer, which illustrates the broad impact of gene regulation by HIF-1 alpha. (bio-techne.com)
  • Semenza G. Dynamic regulation of stem cell specification and maintenance by hypoxia-inducible factors. (ulsu.ru)
  • Prabhakar N., Semenza G. Regulation of carotid body oxygen sensing by hypoxia-inducible factors. (ulsu.ru)
  • Prolyl 4-hydroxylases (P4Hs) have central roles in the synthesis of collagens and the regulation of oxygen homeostasis. (indexindex.com)
  • Hirsilä M., Koivunen P., Günzler V., Kivirikko K., Myllyharju J. Characterization of the human prolyl 4-hydroxylases that modify the hypoxia-inducible factor. (ulsu.ru)
  • The analysis revealed a hypoxia-inducible factor (HIF)-related signature common to succinate dehydrogenase (SDH) and von Hippel-Lindau (VHL) tumors, that differentiated them from RET and neurofibromatosis type 1 cases. (nih.gov)
  • Cell responses to chronic hypoxia are determined by HIF-pool localized in the cytoplasm. (ulsu.ru)
  • Coleman M., Ratcliffe P.J. Oxygen sensing and Hypoxia-induced responses. (ulsu.ru)
  • Recent evidence obtained in mouse models shows its essential role regulating blood cell function through various mechanisms that include pseudohypoxia responses by hypoxia-inducible factor-1α activation, post-translational modifications like succinylation, and communication mediated by succinate receptor 1. (haematologica.org)
  • Interestingly, succinate plays key dual roles during inflammatory responses, leading to net inflammation or anti-inflammation depending on factors like the cellular context. (haematologica.org)
  • Hypoxia-inducible factor-1 (HIF-1) is the central mediator of cellular responses to low oxygen and vital to many aspects of cancer biology. (spandidos-publications.com)
  • The HIFs are transcription factors with a very broad biological significance to many cell and tissue types [ 27 ]. (biomedcentral.com)
  • Hypoxia-inducible factors (HIFs) are key mediators expressed under hypoxic condition and involved in many kinds of disease such as cancer and abnormal angiogenesis. (cd4inhibitors.com)
  • Hypoxia-inducible factors (HIFs), the major transcription regulators for hypoxic cells, are composed primarily of regu- latory alpha-subunits (HIF-1α, HIF-2α, and HIF-3α) [1, 2]. (cd4inhibitors.com)
  • In this study, we demonstrated that Remodelin could not only inhibit the expression of HIF-1α or HIF-2α under hypoxic conditions but also suppress the constitutional expression of HIFs owing to genetic mutation. (cd4inhibitors.com)
  • Previously we found that estrogen aided in this neovasculogenesis via recruitment of bone marrow derived endothelial progenitor cells (BM-EPCs), leading to increased vessel formation and vascular endothelial growth factor (VEGF) production in vivo . (biomedcentral.com)
  • Soluble factors in conditioned media from E 2 treated breast cancer cells also lead to migration and tube formation of human umbilical vein endothelial cells (HUVEC) in vitro . (biomedcentral.com)
  • Further, hypoxia and estrogen are interchangeable as both similarly modulate epithelial-endothelial cell interaction. (biomedcentral.com)
  • Especially, this allows ATP and VEGF (vascular endothelial growth factor) to be synthesized in an oxygen-independent manner, thereby promoting angiogen- esis, cell survival and tumor growth [5]. (cd4inhibitors.com)
  • 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)
  • 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)
  • HIF is primarily regulated through oxygen-dependent proteasomal destruction of the regulatory subunit, HIF-1 alpha or HIF-2 alpha. (ox.ac.uk)
  • Both anabolic phenotype and inflammatory pathology are proposed to be dependent on hypoxia-inducible factor 2 alpha (HIF-2α). (biomedcentral.com)
  • Researchers have understood for numerous years that the hypoxia found in tumors leads to more aggressive and harder to treat disease and ultimately, poor patient outcome. (mdpi.com)
  • Multiple endocrine neoplasia syndrome type 1 (MEN-1), loss-of-function germline mutations in the tumor suppressor gene MEN1 increase the risk of developing pituitary, parathyroid and pancreatic islet tumors, and less commonly thymic carcinoids, lipomas and benign adrenocortical tumors. (intechopen.com)
  • In this model, prolyl hydroxylase 3 (EglN3) abrogation plays a pivotal role, but the molecular mechanisms underlying its inactivation are currently unknown. (nih.gov)
  • Furthermore, telomerase (TERT), cytokines/ligands involved in stem cell trafficking (SDF/CXCR-4), erythropoiesis (EPO), and angiogenesis (VEGF) were increased under hypoxia. (ox.ac.uk)
  • Estrogen treated TG1-1 cells secreted higher levels of VEGF which were comparable to secreted levels from cells grown under hypoxic conditions. (biomedcentral.com)
  • Figure 1 Brief schematics of KSHV-mediated alteration of host cellular metabolic pathways. (frontiersin.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)
  • However, current protocols used to expand CDCs require at least 1 month in vitro to obtain sufficient cells for transplantation. (ox.ac.uk)
  • AIMS: Hypoxia-inducible factor-1 (HIF-1) has been reported to promote tolerance against acute myocardial ischaemia-reperfusion injury (IRI). (ox.ac.uk)
  • PI3K is activated by growth factors resulting in, among others, the activation of Akt and mTOR. (hindawi.com)
  • However, the mechanism through which HIF-1 stabilization actually confers this cardioprotection is not clear. (ox.ac.uk)
  • Succinate inhibits action of prolyl hydroxylases (PHD) and thereby causes stabilization of hypoxia-inducible factor-1α (HIF-1α). (haematologica.org)
  • We report that CDC culture can be optimized by preconditioning the cells under hypoxia (2% oxygen), which may reflect the physiological oxygen level of the stem cell niche. (ox.ac.uk)
  • The quintessential pro-inflammatory cytokine Interleukin-1 (IL-1) canonically triggers a broad spectrum of physiological consequences. (biomedcentral.com)
  • Performed in the lab of UK College of Medicine associate professor Ren Xu, the study found that P4HA1 expression was induced in triple-negative breast cancer, and P4HA1 expression enhanced hypoxia-inducible factor (HIF) 1α stability, thereby increasing cancer stem cell population. (uky.edu)
  • eukaryotic translation elongation factor. (gsea-msigdb.org)
  • Here we show, in articular chondrocytes, that IL-1β-induces primary cilia elongation with alterations to cilia trafficking of arl13b. (biomedcentral.com)
  • Townley-Tilson W., Pi X., Xie L. The Role of Oxygen Sensors, Hydroxylases, and HIF in Cardiac Function and Disease. (ulsu.ru)
  • Under hypoxia, the CDC proliferation rate increased by 1.4-fold, generating 6 × 10(6) CDCs with higher expression of cardiac stem cell and pluripotency gene markers compared to normoxia. (ox.ac.uk)
  • stitute of 11 distinct gene families, which initiate the Carcinogenesis was induced by single tail vein injection of st sequential lcleavage of cyclic adenosine monophosphate MNU on day 1 in each animal. (sagepub.com)
  • Further analysis of independent cohorts of patients with renal carcinoma revealed specific HIF2α gene expression signatures in the context of VHL Ser65Pro or Ser65Trp mutation, showing high correlations with hypoxia and epithelial-mesenchymal transition signaling activities and strong associations with poor prognosis. (biomedcentral.com)
  • Glioblastoma (GBM) is the most common and aggressive type of primary brain tumor 1 . (nature.com)
  • However, cancer cells overcome these controls, in particular by acquiring genetic mutations leading to the activation of oncogenes (pten, myc) or loss of tumor suppressors (p53) [ 1 ]. (hindawi.com)
  • Hypoxia is an important micro-environmental factor in promoting tumor progression. (spandidos-publications.com)
  • 6 3 In fact, one of the first pieces of evidence for a role of succinate in cancer development was provided by the discovery of pseudohypoxia, which refers to activation of hypoxia signaling pathways under normal oxygen levels. (haematologica.org)
  • Molecular intracellular reactions to interval hypoxia are triggered by the prooxidant process activation in the mitochondria of cells. (ulsu.ru)