• The HIF DNA binding complex consists of 2 basic-helix-loop-helix PAS proteins designated alpha and beta subunits. (ox.ac.uk)
  • 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)
  • While mRNA of alfa subunits (HIFs- α) are not altered by exposure to hypoxia, alfa, but not beta, proteins are stabilized by hypoxia. (biomedcentral.com)
  • G-/GMCSF activates the JAK family of receptor tyrosine kinases, which unfolds its activity by not only regulating enzymes and target proteins within its local milieu, but importantly also by activating the STAT family of transcription factors, which subsequently dimerize and translocate to the cell nucleus to regulate gene expression[ 13 ]. (biomedcentral.com)
  • Connective tissue growth factor (CTGF) is regulated by Wnt and bone morphogenetic proteins signaling in osteoblast differentiation of mesenchymal stem cells. (uchicago.edu)
  • Like other TNF-family receptors and the IL-1 receptor, RANK mediates its signal transduction via TNF receptor-associated factor (TRAF) proteins, suggesting that the signaling pathways activated by RANK and other inflammatory cytokines involved in osteoclast differentiation and activation are interconnected. (umassmed.edu)
  • 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)
  • Muscle biopsy hallmarks include perifascicular atrophy, loss of intramuscular capillaries, perivascular and perimysial inflammation and the overexpression of IFN-inducible genes. (nih.gov)
  • The mRNA expression of HIF target genes, namely glucose transporter-1, carbonic anhydrase-9, vascular endothelial growth factor, B-cell lymphoma 2/adenovirus E1B 19-kDa protein-interacting protein 3, prolyl hydroxylase domain-2, and prolyl hydroxylase domain-3, was not significantly altered in NVVs and VVs exposed to hypoxia and treated with doxycycline or MPFF compared with those untreated. (ox.ac.uk)
  • Under hypoxic conditions activates the transcription of over 40 genes, including, erythropoietin, glucose transporters, glycolytic enzymes, vascular endothelial growth factor, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia. (abcam.cn)
  • 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)
  • 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 transcriptional complex hypoxia-inducible factor-1 (HIF-1) has emerged as an important mediator of gene expression patterns in tumors, although the range of responding genes is still incompletely defined. (ox.ac.uk)
  • Identification of novel hypoxia dependent and independent target genes of the von Hippel-Lindau (VHL) tumour suppressor by mRNA differential expression profiling. (ox.ac.uk)
  • Among a group of newly identified VHL target genes the majority but not all were regulated by oxygen, indicating that whilst dysregulation of the HIF system makes a dominant contribution to alterations in transcription, VHL has other influences on patterns of gene expression. (ox.ac.uk)
  • Genes newly defined as targets of the VHL/hypoxia pathway (conditionally downregulated by VHL in normoxic cells) include aminopeptidase A, collagen type V, alpha 1, cyclin G2, DEC1/Stra13, endothelin 1, low density lipoprotein receptor-related protein 1, MIC2/CD99, and transglutaminase 2. (ox.ac.uk)
  • 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)
  • Results suggest HIF-2 may be necessary to maintain hypoxic expression of certain c-Myc regulated genes, possibly by countering the inhibitory effect of HIF-1. (niu.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)
  • 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)
  • This heterodimer binds to HRE (hypoxia responsive components) in promoters of a lot of hypoxia responsive genes, that are including growth factors, angiogenic variables, anti-apoptotic components plus the components involved in anaerobic metabolism [22,23]. (epigenetics-modulation-frontier.com)
  • Hypoxic regulation of lactate dehydrogenase A. Interaction between hypoxia-inducible factor 1 and cAMP response elements. (ox.ac.uk)
  • HIF-1-dependent regulation of hypoxic induction of the cell death factors BNIP3 and NIX in human tumors. (ox.ac.uk)
  • Using cDNA arrays and serial analysis of gene expression, we found that hypoxia induces up-regulation of BNIP3 and its homologue, Nip3-like protein X. Analysis of human carcinoma cell lines showed that they are hypoxically regulated in many tumor types, as well as in endothelial cells and macrophages. (ox.ac.uk)
  • Regulation was hypoxia inducible factor-1-dependent, and hypoxia inducible factor-1 expression was suppressed by von Hippel-Lindau protein in normoxic cells. (ox.ac.uk)
  • 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)
  • In renal carcinoma cells that are defective for the von Hippel-Lindau (VHL) tumor suppressor, up-regulation of these CAs is associated with loss of regulation by hypoxia, consistent with the critical function of pVHL in the regulation of HIF-1. (ox.ac.uk)
  • Further studies of CA9 defined a HIF-1-dependent hypoxia response element in the minimal promoter and demonstrated that tight regulation by the HIF/pVHL system was reflected in the pattern of CA IX expression within tumors. (ox.ac.uk)
  • Regulation of hypoxia-inducible factor is preserved in the absence of a functioning mitochondrial respiratory chain. (ox.ac.uk)
  • Regulation occurs principally through the alpha subunits, which are stabilized and activated in hypoxia. (ox.ac.uk)
  • Extensive regulation of the non-coding transcriptome by hypoxia: role of HIF in releasing paused RNApol2. (ox.ac.uk)
  • 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)
  • The regulation of interleukin-8 by hypoxia in human macrophages--a potential role in the pathogenesis of the acute respiratory distress syndrome (ARDS). (ox.ac.uk)
  • These research underscore the importance of hypoxia inducible factor-1alpha (HIF-1a) in regulation of replicative and drug-induced senescence below hypoxic conditions, which can be commonly found in huge portions of tumor tissue identified in all the mammals. (epigenetics-modulation-frontier.com)
  • Regulation of carotid body oxygen sensing by hypoxia-inducible factors. (uchicago.edu)
  • Hypoxia-inducible factors (HIFs) are transcription factors crucial for regulating the cellular response to low oxygen. (niu.edu)
  • Hypoxia-inducible factors (HIFs) are responsible for the transcriptional responses to hypoxic stress. (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)
  • 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 hydroxylation of HIF1A proline residue also regulates its ability to associate with co-activators under hypoxia. (wikipedia.org)
  • Recently, prolyl hydroxylation was identified as a key regulatory event that targets the HIF-1alpha subunit for proteasomal degradation via the pVHL ubiquitination complex. (nih.gov)
  • Asparaginyl hydroxylation of the Notch ankyrin repeat domain by factor inhibiting hypoxia-inducible factor. (ox.ac.uk)
  • The stability and activity of hypoxia-inducible factor (HIF) are regulated by the post-translational hydroxylation of specific prolyl and asparaginyl residues. (ox.ac.uk)
  • We show that the HIF asparaginyl hydroxylase, factor inhibiting HIF (FIH), also catalyzes hydroxylation of highly conserved asparaginyl residues within ankyrin repeat (AR) domains (ARDs) of endogenous Notch receptors. (ox.ac.uk)
  • 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)
  • Furthermore, concentrations of rotenone that maximally inhibited respiration did not affect HIF activation by hypoxia. (ox.ac.uk)
  • Both the pattern of cytokine expression and transcription factor activation by hypoxia was different to that seen with endotoxin.ConclusionsRapidly raised intrapulmonary IL-8 levels are associated with ARDS progression in patients with major trauma. (ox.ac.uk)
  • The RVSP of mice lacking HIF-2α in pulmonary endothelium after exposure to hypoxia was not significantly different from normoxic WT mice and much lower than the RVSP values seen in WT littermate controls and mice with pulmonary endothelial deletion of HIF-1α exposed to hypoxia. (cam.ac.uk)
  • These recruited monocyte-derived macrophages also protect lung function by their heightened production of antipathogen factors and active phagocytosis of cellular debris (Aegerter et al. (biomedcentral.com)
  • In human monocyte derived macrophages hypoxia rapidly upregulated IL-8 protein (within 2 hours) and mRNA expression (within 30 mins). (ox.ac.uk)
  • The effects of doxycycline and micronized purified flavonoid fraction on human vein wall remodeling are not hypoxia-inducible factor pathway-dependent. (ox.ac.uk)
  • 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)
  • This study provides evidence on pathways to be investigated to elucidate the interplay between FOXP1, ER-alpha and HIF-1alpha in hormone dependent cancers. (ox.ac.uk)
  • The von Hippel-Lindau tumour suppressor gene (VHL) targets hypoxia inducible factor (HIF)-alpha subunits for ubiquitin dependent proteolysis. (ox.ac.uk)
  • 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)
  • 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)
  • 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)
  • Hypoxia stimulates hypoxia inducible factor (HIF)-dependent expression of CXCL12 and KITL promoting mobilization from the bone marrow and recruitment to primary tumor and metastatic sites of CXCR4 + CD11b + bone marrow-derived cells and KITbCD11b + cells assisting vasculogenesis and metastasis respectively (Kuonen et al. (biomedcentral.com)
  • Hypoxic conditions further increased GLUT1 expression levels in HCC cells, and this induction was dependent on the activation of the transcription factor hypoxia-inducible factor-1alpha. (uni-regensburg.de)
  • HIF1 is often a transcription issue, consisting of two subunits, an a subunit, which levels are oxygen dependent and b subunit which is constitutively expressed. (epigenetics-modulation-frontier.com)
  • The results obtained indicate that alpha6beta1 is necessary for VEGF expression because the ability of hypoxia to activate HIF-1 and to stimulate VEGF transcription in MDA-MB-435 cells is dependent on alpha6beta1 expression by a mechanism that involves protein kinase C-alpha. (umassmed.edu)
  • 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)
  • Solid tumors contain regions of hypoxia, a physiological stress that can activate cell death pathways and, thus, result in the selection of cells resistant to death signals and anticancer therapy. (ox.ac.uk)
  • Northern blotting and in situ hybridization analysis has revealed that these factors are highly expressed in human tumors compared with normal tissue and that BNIP3 is up-regulated in perinecrotic regions of the tumor. (ox.ac.uk)
  • Over 90% of necrotic and 30% of non-necrotic tumors expressed at least one hypoxia marker. (ox.ac.uk)
  • Survival analysis of 53 cases found that the subset of tumors with stromal hypoxia exhibit better prognosis (p=0.027). (ox.ac.uk)
  • The use of several hypoxia markers may identify a continuum of hypoxia in tumors, which can be sub-classified by different co-expression patterns. (ox.ac.uk)
  • Tumors with exclusively cytoplasmic expression of FOXP1 were linked with deep myometrial invasion and hypoxia-inducible factors 1alpha (HIF-1alpha) expression. (ox.ac.uk)
  • Hypoxia represents a major driver of the cancer phenotype in solid tumors, especially those of hepatic origin. (niu.edu)
  • In response to hypoxia, tumors activate a general adaptive response allowing their growth under unfavourable conditions. (biomedcentral.com)
  • Several types of non-hematopoietic tumors secrete hematopoietic colony stimulating factors, which act on myeloid cells and tumor cells[ 7 ]. (biomedcentral.com)
  • The human HIF1A gene encodes for the alpha subunit, HIF1A of the transcription factor hypoxia-inducible factor (HIF1). (wikipedia.org)
  • To investigate the relation between necrosis and hypoxia in breast cancer we examined the expression of hypoxia-associated markers HIF1, CA IX and GLUT1 by immunohistochemistry in 97 invasive ductal carcinomas. (ox.ac.uk)
  • Here, we show that hypoxia induces corticosteroid-insensitive inflammation via reduced transcription of histone deacetylase-2 (HDAC2) in lung epithelial and macrophage cells. (tmu.edu.tw)
  • 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)
  • To test this model the induction of the HIF-1alpha subunit and the HIF target gene, glucose-transporter-1, was examined in a variety of mutant cells that lacked mitochondrial DNA (rho0) or had other genetic defects in mitochondrial respiration. (ox.ac.uk)
  • HIF induction by hypoxia was essentially normal in all cells tested. (ox.ac.uk)
  • Hydrogen peroxide production was measured by the luminol/peroxidase method and found to be reduced in rho0 versus wild-type cells and reduced by hypoxia in both rho0 and wild-type cells. (ox.ac.uk)
  • We undertook integrated genomic analyses of both non-coding and coding transcripts using massively parallel sequencing and interfaced this data with pan-genomic analyses of hypoxia-inducible factor (HIF) and RNApol2 binding in hypoxic cells. (ox.ac.uk)
  • 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)
  • Estrogen treated TG1-1 cells secreted higher levels of VEGF which were comparable to secreted levels from cells grown under hypoxic conditions. (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)
  • Growing evidence suggests the amino acid glutamine, an important molecular currency for both energy producing reactions and biosynthetic pathways, plays an enhanced role in cancer cells under hypoxia. (niu.edu)
  • More importantly, Remodelin could also inhibit the constitutional expression of HIF-1α and HIF-2α in VHL mutant 786-0 cells. (cd4inhibitors.com)
  • In addition, the number and the migratory activity of these cells are inversely correlated with risk factors such as hypertension, hypercholesterolemia, diabetes, and metabolic syndrome. (intechopen.com)
  • Such treatment was associated with upregulation of invasion- and inflammation-promoting soluble factors, such as matrix metalloproteinase 2 (MMP2), its activator MMP14, tissue inhibitors of matrix metalloproteinase 2 (TIMP2), chemokine ligand 2 (CCL2), and urokinase-type plasminogen activator (uPA), the latter two being linked to the recruitment of the monocytic cells. (biomedcentral.com)
  • RNA interference-mediated gene silencing of vascular endothelial growth factor in colon cancer cells. (uchicago.edu)
  • The glucose transporter isoform 1 (GLUT1) gene encodes a key rate-limiting factor in glucose transport into cancer cells. (uni-regensburg.de)
  • This is because cancer cells maintain high basal level of ROS, thus they are vulnerable to any further increase in ROS (Fig. 1 ). (degruyter.com)
  • JAG cells, juxtaglomerular showing can permanently class involved by producing of NOTCH3 to YBX1( YB 1)( Rauen et al. (evakoch.com)
  • Based on the hypothesis that alpha6beta1 is necessary for the survival of these cells in the tumor microenvironment, we report here that hypoxia protects these cells from apoptosis induced by serum deprivation and that hypoxia-mediated protection requires alpha6beta1 expression. (umassmed.edu)
  • We investigated the influence of alpha6beta1 on vascular endothelial growth factor (VEGF) expression because autocrine VEGF is necessary for the survival of serum-deprived cells in hypoxia. (umassmed.edu)
  • To understand the functional interactions between the TrkA and p75 nerve growth factor (NGF) receptors, we stably transfected LAN5 neuroblastoma cells with an expression vector for ET-R, a chimeric receptor with the extracellular domain of the epidermal growth factor receptor (EGFR), and the TrkA transmembrane and intracellular domains. (umassmed.edu)
  • Necrosis and hypoxia in invasive breast carcinoma. (ox.ac.uk)
  • Loss of expression and nuclear/cytoplasmic localization of the FOXP1 forkhead transcription factor are common events in early endometrial cancer: relationship with estrogen receptors and HIF-1alpha expression. (ox.ac.uk)
  • Mitochondria are an important source of ROS, and in one model it has been proposed that hypoxia increases the generation of ROS at complex III in the mitochondrion and that this signal acts through a transduction pathway to stabilize HIF-1alpha and to activate HIF. (ox.ac.uk)
  • Semaphorins were originally identified in the nervous system for their ability to regulate axon guidance through the interaction with their receptors, plexins and neuropilins [ 1 ]. (biomedcentral.com)
  • Recent studies indicate that some hematopoietic growth factors, namely granulocyte macrophage colony stimulating factor (GMCSF) and granulocyte colony stimulating factor (GCSF), are abundantly released in the tumor microenvironment and play a key role in regulating tumor-nerve interactions and tumor-associated pain by activating receptors on dorsal root ganglion (DRG) neurons. (biomedcentral.com)
  • ALOX5 arachidonate 5-lipoxygenase: macrophages infected with Candida albicans, Aspergillus flavus or Aspergillus fumigatus or treated with Curdlan, a selective agonist of pattern recognition receptor for fungi Dectin-1, displays increased expression of ALOX5, ALOX15 and PTGS2 Karnam et al, 2015 . (polygenicpathways.co.uk)
  • APOBEC3F apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3F: Candida albicans enhanced the production of the CCR5-interacting chemokines CCL3, CCL4, and CCL5, and stimulates the production of interferon-a and the restriction factors APOBEC3G, APOBEC3F, and tetherin (BST2) in macrophages Rodriguez et al, 2013 . (polygenicpathways.co.uk)
  • BST2 bone marrow stromal cell antigen 2 (Tetherin): Candida albicans enhanced the production of the CCR5-interacting chemokines CCL3, CCL4, and CCL5, and stimulates the production of interferon-a and the restriction factors APOBEC3G, APOBEC3F, and tetherin (BST2) in macrophages Rodriguez et al, 2013 . (polygenicpathways.co.uk)
  • Acute hypoxia, a clinically relevant stimulus, rapidly and selectively upregulates IL-8 in macrophages associated with a novel pattern of transcription factor activation. (ox.ac.uk)
  • We recently reported that in vitro exposure of non-VV (NVVs) and VVs to hypoxic conditions activates the hypoxia-inducible factor (HIF) pathway. (ox.ac.uk)
  • CONCLUSIONS: Doxycycline and MPFF at a concentration corresponding to a therapeutic dose do not alter the activation of the HIF pathway in NVV and VV organ cultures exposed to hypoxia. (ox.ac.uk)
  • 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)
  • Combined the network analysis, molecular docking and in-vitro experiments, the results firstly demonstrated that the treatment effect of DGP on ONFH may be closely related to HIF-1α, VEGFA and HIF-1 signaling pathway. (researchsquare.com)
  • The results indicated that DGP may exert the effect on ONFH targeting on HIF-1α and VEGFA via HIF-1 signaling pathway. (researchsquare.com)
  • Hypoxia-inducible factor (HIF) mediates a large number of transcriptional responses to hypoxia and has an important role in processes that include angiogenesis and erythropoiesis. (ox.ac.uk)
  • Estrogen mediates its effects by binding to its cognate estrogen receptor(s), either estrogen receptor alpha (ERα) or estrogen receptor beta (ERβ), leading to ER dimerization and association with various co-factors. (biomedcentral.com)
  • Hypoxia downregulated a range of other proinflammatory mediators, including MCP-1 and TNF-alpha. (ox.ac.uk)
  • 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)
  • These studies define a new class of HIF-1-responsive gene, the activation of which has implications for the understanding of hypoxic tumor metabolism and which may provide endogenous markers for tumor hypoxia. (ox.ac.uk)
  • Family member HIF-1 has been well studied, however, recent evidence suggests HIF-2 may have a regulatory role in amino acid transport and metabolism under hypoxia. (niu.edu)
  • This growth factor also stimulates production of collagens, proteoglycans, elastin, fibronectin, tenascin and thrombospondin, diminishes production of extracellularly active neutral endoproteinases belonging to the matrix metalloproteinase (MMP) and serine proteinase families, and stimulates production of endogenous MMP inhibitors (tissue inhibitor of metallo-proteinase [TIMP]) and serpins (plasminogen activator inhibitor-1). (biomedcentral.com)
  • Breast cancer is recognized as the most common type of cancer in women and its development is associated with many risk factors such as diet, alcohol consumption, child bearing, breast feeding, oral contraception, as well as underlying genetic predisposition. (biomedcentral.com)
  • Under normoxic conditions HIF-1 alpha has a short half-life. (abcam.cn)
  • In comparison with vascular endothelial growth factor mRNA, expression of CA IX demonstrated a similar, although more tightly circumscribed, pattern of expression around regions of necrosis and showed substantial although incomplete overlap with activation of the hypoxia marker pimonidazole. (ox.ac.uk)
  • 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)
  • 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)
  • Functions as a master transcriptional regulator of the adaptive response to hypoxia. (abcam.cn)
  • These analyses revealed that all classes of RNA are profoundly regulated by hypoxia and implicated HIF as a major direct regulator of both the non-coding and coding transcriptome, acting predominantly through release of pre-bound promoter-paused RNApol2. (ox.ac.uk)
  • Here we show that pulmonary endothelial HIF-2α is a critical regulator of hypoxia-induced pulmonary arterial hypertension. (cam.ac.uk)
  • Deletional and mutational analysis of the function of mouse LDH-reporter fusion gene constructs in transient transfection assays defined three domains, between -41 and -84 base pairs upstream of the transcription initiation site, which were crucial for oxygen-regulated expression. (ox.ac.uk)
  • Hypoxia, a condition of oxygen deprivation, is considered a hallmark of tumor microenvironment regulating several pathways and promoting cancer progression and resistance to therapy. (biomedcentral.com)
  • Hypoxia (low oxygen concentration) and nutrient deprivation, caused by inappropriate blood supply, represent important hallmarks of tumor microenvironment. (biomedcentral.com)
  • In fact, HIF-1α is a major factor for regulating tumor microenvironment (TME) for tumor cell survival and angiogenesis [6, 7]. (cd4inhibitors.com)
  • 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)
  • 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)
  • Hypoxia induced HIF-1 expression, but cobaltous ions and desferrioxamine did not mimic hypoxic IL-8 induction. (ox.ac.uk)
  • plosone.orgHIF-1 Alpha Modulates Oncogene-Induced Senescenceinduction of senescence, at the very least in component by induction of telomere shortening [19]. (epigenetics-modulation-frontier.com)
  • We conclude that stromal and epithelial hypoxia may have different biological backgrounds and that stromal hypoxia may affect survival. (ox.ac.uk)
  • Further, hypoxia and estrogen are interchangeable as both similarly modulate epithelial-endothelial cell interaction. (biomedcentral.com)
  • There coalesce roles that NOTCH2 Actively binds with breast inner tyrosine 1-beta( HNF1B) in wtih response( Massa et al. (evakoch.com)
  • We propose a mechanism whereby chronic hypoxia enhances HIF-2α stability, which causes increased arginase expression and dysregulates normal vascular NO homeostasis. (cam.ac.uk)
  • Endothelial HIF-2α deletion also protected mice from hypoxia remodeling. (cam.ac.uk)
  • Other profibrotic, collagen synthesis stimulating cytokines include endothelin, interleukin (IL)-1 and mast cell tryptase. (biomedcentral.com)
  • Hypoxia is central to both ischaemic and neoplastic diseases. (ox.ac.uk)
  • Taken together with the fact that 60-70% of human breast cancers are estrogen receptor-alpha positive[ 7 ], the evidence suggests an etiological significance of estrogen in breast cancer initiation and progression. (biomedcentral.com)
  • In the last years a huge amount of data has been obtained shedding novel insights on the mechanisms through which hypoxia affects tumor progression and response to therapy. (biomedcentral.com)
  • Some cytokines act as competence rather than progression factors, some lack secretory signals, and some must be processed and released from the pericellular matrix or basement membranes (eg transforming growth factor beta [TGF-β ] binding to chondroitin or the keratan sulfate of biglycan, decorin and fibromodulin, or basic fibroblast growth factor and platelet derived growth factor binding to the heparin sulfate of glypican, perlecan and syndecan). (biomedcentral.com)
  • 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)
  • We identified putative hypoxia response elements (HRE) in RIG-I regulatory regions and luciferase assays confirmed that RIG-I is a new HIF-inducible gene. (nih.gov)
  • 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)
  • 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)
  • In hypoxia-independent ways, HIF1A expression may be upregulated through a redox-sensitive mechanism. (wikipedia.org)
  • The aim of this work was to study if RIG-I expression may be modulated by hypoxia using an in vitro approach. (nih.gov)
  • Cell transfection with a constitutive RIG-I expression vector increased levels of phospho-IRF-3, indicating that RIG-I promotes binding of transcription factors to the enhancer sequence of IFN. (nih.gov)
  • The veins were analyzed for HIF-1α, HIF-2α, and their target gene expression, with real-time polymerase chain reaction and Western blot. (ox.ac.uk)
  • RESULTS: Treatment of NVV organ cultures exposed to hypoxia with doxycycline or MPFF did not significantly alter the expression of HIF-1α and HIF-2α messenger (m)RNA and protein compared with untreated. (ox.ac.uk)
  • Doxycycline also did not significantly affect the expression of HIF-1α and HIF-2α mRNA and protein in VVs exposed to hypoxia compared with untreated VVs. (ox.ac.uk)
  • However, MPFF significantly reduced the expression of HIF-1α but not HIF-2α mRNA in VVs exposed to hypoxia compared with untreated VVs. (ox.ac.uk)
  • Interestingly, the reduction of the expression of HIF-1α mRNA in VVs by MPFF was not reflected at the protein level. (ox.ac.uk)
  • 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)
  • We also observed expression of hypoxia associated markers in tumor stroma. (ox.ac.uk)
  • On the other hand, the presence of nuclear FOXP1 expression was significantly linked with ER-alpha reactivity. (ox.ac.uk)
  • We will also describe evidence about the ability of semaphorins to affect the expression and activity of transcription factors activated by hypoxia, such as hypoxia-inducible factor-1. (biomedcentral.com)
  • 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)
  • 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)
  • Acute hypoxia also increased rabbit alveolar macrophage IL-8 expression. (ox.ac.uk)
  • however, the specific role of pulmonary endothelial HIF expression in this process, and in the physiological process of vasoconstriction in response to hypoxia, remains unclear. (cam.ac.uk)
  • The transcription factor HIF-1 plays an important role in cellular response to systemic oxygen levels in mammals. (wikipedia.org)
  • Hypoxia-inducible factor 1 (HIF-1) plays a central role in cellular adaptation to changes in oxygen availability. (nih.gov)
  • The FOXP1 gene has been identified as a new member of the winged helix family of transcription factors that have important roles in cellular transformation, differentiation and proliferation. (ox.ac.uk)
  • Therefore, this study generated a series of human liver cancer cell lines either lacking or overexpressing the HIF-2 alpha subunit in order to examine its potential role in cellular glutamine transport. (niu.edu)
  • However, the non-coding transcriptional response to hypoxia is largely uncharacterized. (ox.ac.uk)
  • A second dose of DETA NO, administered after 4 hours, did not pro long the growth inhibition, suggesting that stress response factors and NO defence mecha nisms may have been activated by the first dose. (igf-1rinhibitors.com)
  • These data offer new insight into the role of pulmonary endothelial HIF-2α in regulating the pulmonary vascular response to hypoxia. (cam.ac.uk)
  • Hypoxia also decreased marks of Ras-induced DNA harm response (DDR) in both cell lines via downregulation of ATM/ATR, Chk1, and Chk2 also as decreased c-H2AX positivity. (epigenetics-modulation-frontier.com)
  • On the other hand, the number of circulating hEPC is increased in hypoxia or acute myocardial infarction (AMI). (intechopen.com)
  • Acute hypoxia may represent one of potentially several proinflammatory stimuli responsible for rapid intrapulmonary IL-8 generation in patients at-risk of ARDS. (ox.ac.uk)
  • Expressed sequence tag (EST) analysis and developmental polymerase chain reaction (PCR) studies demonstrated that Ov-phy-1 was expressed in L3 and adult parasites. (embl.de)
  • Pulmonary endothelial deletion of arginase-1, a downstream target of HIF-2α, likewise attenuated many of the pathophysiological symptoms associated with hypoxic pulmonary hypertension. (cam.ac.uk)