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  • Cells
  • Cartilage cells, the chondrocytes, have adapted to this and actually use hypoxia to drive tissue-specific functions. (ox.ac.uk)
  • residues
  • The peptide binding domain spans residues 140-215 of the α subunit, and consists of a concave surface lined with multiple tyrosine residues which interact favorably with the proline-rich substrate. (wikipedia.org)
  • The active site consists of Fe2+ bound to two histidine residues and one aspartate residue, a characteristic shared by most 2-oxoglutarate-dependent dioxygenases. (wikipedia.org)
  • PHD2
  • PHD2 mRNA was induced by hypoxia in the liver and PHD3 mRNA in liver, testis and heart. (ox.ac.uk)
  • Inducibility of PHD2 and 3 by hypoxia and ischemia in vivo has important implications both for the pathophysiology of conditions where oxygen supply is deranged and for attempts to manipulate the HIF system therapeutically. (ox.ac.uk)
  • INTRODUCTION: The purpose of the present study was to investigate the relationship of expression of hypoxia inducible factor (HIF)-1α-modifying enzymes prolyl hydroxylase (PHD)1, PHD2 and PHD3 to response of tumours and survival in breast cancer patients enrolled in a phase II trial of neoadjuvant anthracycline and tamoxifen therapy. (ox.ac.uk)
  • METHODS: The expression of PHD1, PHD2 and PHD3 together with HIF-1α and the HIF-inducible genes vascular endothelial cell growth factor (VEGF) and carbonic anhydrase IX were assessed by immunohistochemistry using a tissue microarray approach in 211 patients with T2-4 N0-1 breast cancer enrolled in a randomised trial comparing single-agent epirubicin versus epirubicin and tamoxifen as the primary systemic treatment. (ox.ac.uk)
  • PHD2 is a member of the non-haem Fe(II) and 2-oxoglutarate (2OG)-dependent dioxygenases. (wikipedia.org)
  • 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)
  • Substrate analog peptides have also been developed to exhibit inhibitory selectivity for PHD2 over factor inhibiting HIF (FIH), for which some other PHD-inhibitors show overlapping specificity. (wikipedia.org)
  • Transforming growth factor beta1 induces hypoxia-inducible factor-1 stabilization through selective inhibition of PHD2 expression. (semanticscholar.org)
  • Mice
  • Adult C57 mice exposed to hypoxia from P3 to P11 exhibited learning impairment and increased anxiety. (nih.gov)
  • In this study, we assess whether inhibiting the placental growth factor (PlGF) could offer a therapeutic option in mice with hepatocellular carcinoma and cholangiocarcinoma. (uclouvain.be)
  • vascular
  • The prolyl hydroxylase enzymes are positively associated with hypoxia-inducible factor-1α and vascular endothelial growth factor in human breast cancer and alter in response to primary systemic treatment with epirubicin and tamoxifen. (ox.ac.uk)
  • Double labeling with anti-CD31 (red fluorescence) and anti-HIF-1α (green fluorescence) reveals a low baseline HIF-1α expression in SVZ vasculature and neuropils under normoxia (Nx) (slight orange fluorescence in the vascular compartment and a slight green fluorescence in the neuropil), which is induced after hypoxia (Hx) (intense orange fluorescence in the vascular compartment and increased green fluorescence in the neuropil). (nih.gov)
  • BACKGROUND: Hypertension (HTN) may lead to left ventricular hypertrophy and vascular dysfunction, which are independent factors for adverse cardiovascular outcomes. (biomedsearch.com)
  • PlGF is a homologue of the vascular endothelial growth factor, which is only involved in pathological angiogenesis, therefore, its inhibition does not induce adverse effects. (uclouvain.be)
  • Hypoxia-inducible factor (HIF), a transcriptional factor composed of two subunits (α and β), plays a key role in this process, activating proangiogenic factors such as vascular endothelial growth factor (VEGF). (aacrjournals.org)
  • Kaposi sarcoma (KS) is a highly vascular tumor that releases large amounts of VEGF and for which we have recently described an essential role for the insulin-like growth factor (IGF) system. (aacrjournals.org)
  • Hypoxia plays an important role for expansion of the vascular bed both in normal and in tumor tissue. (aacrjournals.org)
  • EGLN1
  • EGLN1 is the most important isozyme under normoxia and, through regulating the stability of HIF1, involved in various hypoxia-influenced processes such as angiogenesis in retinal and cardiac functionality. (proteopedia.org)
  • regulation
  • We have investigated the organ distribution of the PHDs in the rat, their regulation by hypoxia and changes in local expression after experimental myocardial infarction using RNase protection assays, in situ hybridization and immunohistochemistry. (ox.ac.uk)
  • We demonstrated in CD3-positive human T cells accumulating in inflammatory tissue expression of the hypoxia-inducible factor-1α (HIF-1α), indicating a role of hypoxia-mediated signals in regulation of T cell function. (jimmunol.org)
  • Taken together, we propose that hypoxia is a critical determinant of survival of the activated T cells via the HIF-1α-AM cascade, defining a previously unknown mode of regulation of peripheral immunity. (jimmunol.org)
  • The objective of this study was to analyze the expression and regulation of prolyl hydroxylase domain (PHD) enzymes and factor-inhibiting HIF-1α (FIH-1), which regulate cellular HIF levels, and to study the roles of these enzymes in RA fibroblast-like synoviocytes (RA FLS). (ox.ac.uk)
  • In consequence, up-regulation of HIF in tumors is not just a response of the tissue to hypoxia but represents a step in the oncogenic transformation process and it is a driving force in tumoral neovascularization, at least partially via stimulation of VEGF expression. (aacrjournals.org)
  • Hypoxia-mediated regulation of macrophage functions in pathophysiology. (semanticscholar.org)
  • adaptation
  • Human adaptation to the hypoxia of high altitude: the Tibetan paradigm from the pregenomic to the postgenomic era. (ox.ac.uk)
  • survival
  • Long-term oxygen therapy improves survival in patients with severe hypoxia. (bioportfolio.com)
  • Using mouse strains found to span the range of responsiveness to chronic hypoxia, we correlated differential NSC survival and self-renewal with differences in behavior. (nih.gov)
  • 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)
  • expression
  • organ distribution and changes in expression following hypoxia and coronary artery ligation. (ox.ac.uk)
  • These were accompanied by increased myocardial expression of hypoxia-inducible factor (HIF)-1α, inflammation, and microvascular remodeling, including increased density of epicardial microvessels (20-200 µm), as well as cardiac diastolic dysfunction, all of which improved by reversal of HTN. (biomedsearch.com)
  • Their expression in tumor tissue but not in most of the normal tissues is mainly considered to reflect the relative hypoxia in a rapidly growing tissue ( 12 ). (aacrjournals.org)
  • In hypoxia-independent ways, HIF1A expression may be upregulated through a redox-sensitive mechanism. (wikipedia.org)
  • differentiation
  • C57 NSCs exhibited blunted stromal-derived factor 1-induced migratory responsiveness, decreased matrix metalloproteinase-9 activity, and increased neuronal differentiation. (nih.gov)
  • It has been shown that hypoxia inhibits adipogenic differentiation ( 14 , 15 ), which may further enhance adipocyte hypertrophy due to inadequate de novo adipogenesis ( 16 ). (frontiersin.org)
  • Altitude
  • Several projects in high altitude research in environments with a low oxygen partial pressure (hypobaric hypoxia) leading to hypoxemia showed, that cerebral perfusion and cerebral performa. (bioportfolio.com)
  • Integration of studies at the genomic level with functional molecular studies and studies in systems physiology has the potential to provide further understanding of human evolution in response to high-altitude hypoxia. (ox.ac.uk)
  • tissue
  • Extensive work has been done using various diet-induced obesity models to demonstrate an important role of hypoxia-induced signaling in adipose tissue and its impact on adipose functions related to adipogenesis, insulin sensitivity, and inflammation. (frontiersin.org)
  • Under obese conditions, O 2 concentrations in adipose tissue can be negatively affected by a number of factors. (frontiersin.org)
  • As a result of these and other changes, insufficient oxygenation, i.e., hypoxia occurs in adipose tissue under pathologically obese conditions. (frontiersin.org)
  • Such direct evidence indicates that adipose tissue hypoxia is a common pathological feature of obese subjects. (frontiersin.org)
  • Increasing amounts of evidence nonetheless suggest that hypoxia can exert profound impact on adipose tissue function. (frontiersin.org)
  • Hypoxia affects glucose homeostasis, lipid metabolism, and production of adipokines and pro-inflammatory cytokines in adipose tissue ( 7 , 10 , 17 ). (frontiersin.org)
  • coronary
  • Interestingly, this observation is consistent with the clinical evidence showing that obesity is often associated with ventricular hypertrophy and dysfunction as well as congestive heart failure independent of other well-established risk factors including diabetes, hypertension, and coronary artery disease. (frontiersin.org)