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Definition
 
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Cell Hypoxia definition: A condition of decreased oxygen content at the cellular level.
Myocardial Ischemia definition: A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (CORONARY ARTERY DISEASE), to obstruction by a thrombus (CORONARY THROMBOSIS), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (MYOCARDIAL INFARCTION).
Ischemic Heart Disease definition: A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries, to obstruction by a thrombus, or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (myocardial infarction).
myocardial ischemia/hypoxia definition: blood deficiency in the myocardium caused by a constriction or obstruction of its blood vessels; frequently occurs in conjunction with hypoxia, which is reduction in oxygen supply.
cerebral ischemia/hypoxia definition: localized reduction of blood flow to brain tissue due to arterial obstruction or systemic hypoperfusion; frequently occurs in conjunction with brain hypoxia, which is reduction in brain oxygen supply; severe hypoxia is referred to as anoxia.
hypoxia inducible factor 1 definition: nuclear factor whose DNA binding activity is induced by hypoxia.
Hypoxia-Inducible Factor-1 definition: Hypoxia-inducible factor-1 (HIF1) is a transcription factor found in mammalian cells cultured under reduced oxygen tension that plays an essential role in cellular and systemic homeostatic responses to hypoxia. HIF1 is a heterodimer composed of a 120-kD HIF1-alpha subunit complexed with a 91- to 94-kD HIF1-beta subunit.
Hypoxia-Inducible Factor 1 definition: A basic helix-loop-helix transcription factor that plays a role in APOPTOSIS. It is composed of two subunits: ARYL HYDROCARBON RECEPTOR NUCLEAR TRANSLOCATOR and HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT.
hypoxia definition: reduction of oxygen supply to tissue below physiological level.
hypoxia definition: Having too little oxygen.
hypoxic definition: Having too little oxygen.
Hypoxia definition: A decrease in the amount of oxygen in the body. Symptoms range from mild (impaired judgment, memory loss, impaired motor coordination) to severe (seizures and coma).
Hypoxic definition: Status of decreased oxygen in inspired gases, arterial blood, or tissues. -- 2003
Fetal Hypoxia definition: Hypoxia in utero, caused by conditions such as inadequate placental function (often abruptio placentae), preeclamptic toxicity, prolapse of the umbilical cord, or complications from anesthetic administration.
Hypoxia in Utero definition: Caused by conditions such as inadequate placental function (often abruptio placentae), preeclamptic toxicity, prolapse of the umbilical cord, or complications from anesthetic administration.
Fetal Hypoxia definition: Deficient oxygenation of FETAL BLOOD.
Hypoxia Up-Regulated 1 Protein definition: Highly expressed in secretory tissues (liver and pancreas) by human HYOU1 Gene (HSP70 Family), hypoxia-induced 999-aa (precursor) 150 kD Hypoxia Up-Regulated 1 Protein is an endoplasmic reticulum cytoprotectant in oxygen deprivation that may act as a chaperone with GRPs and participate in protein folding and secretion. ORP150 contains a C-terminal KNDEL sequence and N-terminal similarity to HSP70 ATPase domain. ORP150 suppression is associated with accelerated apoptosis. ORP150 expression in neurons suppresses caspase-3-like activity and enhances BDNF under hypoxia signaling. Elimination of the signal peptide through an alternative translation site may generate a cytosolic housekeeping protein. (NCI)
hypoxia neonatorum definition: reduction of oxygen supply to tissues in newborns that is below physiological levels.
liver ischemia/hypoxia definition: blood deficiency in the liver caused by a constriction or obstruction of its blood vessels; frequently occurs in conjunction with hypoxia, which is reduction in oxygen supply.
lung ischemia/hypoxia definition: blood deficiency in the lungs caused by a constriction or obstruction of its blood vessels; frequently occurs in conjunction with hypoxia, which is reduction in oxygen supply.
renal ischemia/hypoxia definition: blood deficiency in the kidney caused by a constriction or obstruction of its blood vessels, or oxygen concentration below physiological levels.
respiratory hypoxia definition: not enough oxygen in inspired air.
Hypoxia-Ischemia, Brain definition: A disorder characterized by a reduction of oxygen in the blood combined with reduced blood flow (ISCHEMIA) to the brain from a localized obstruction of a cerebral artery or from systemic hypoperfusion. Prolonged hypoxia-ischemia is associated with ISCHEMIC ATTACK, TRANSIENT; BRAIN INFARCTION; BRAIN EDEMA; COMA; and other conditions.
embryo/fetus hypoxia definition: oxygen deficiency in the embryo or fetus.
response to hypoxia definition: A change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus indicating lowered oxygen tension. Hypoxia, defined as a decline in O2 levels below normoxic levels of 20.8 - 20.95%, results in metabolic adaptation at both the cellular and organismal level. [GOC:hjd]
HYOU1 Gene definition: This gene plays in the regulation of cellular response to ischemic stress conditions.
Aryl Hydrocarbon Receptor Nuclear Translocator definition: Aryl Hydrocarbon Receptor Nuclear Translocator, encoded by the ARNT gene, heterodimers with HIF1A or EPAS1/HIF2A and functions as a transcriptional regulator of the adaptive response to hypoxia. Efficient DNA binding requires dimerization with another bHLH protein. This nuclear protein is also required for activity of the Ah (dioxin) receptor and for the ligand-binding subunit to translocate from the cytosol to the nucleus after ligand binding. The complex then initiates transcription of genes involved in the activation of PAH procarcinogens. (From Swiss-Prot and LocusLink)
Angiogenesis Pathway definition: Vascular endothelial growth factor (VEGF) plays a key role in physiological blood vessel formation and pathological angiogenesis such as tumor growth and ischemic diseases. Hypoxia is a potent inducer of VEGF in vitro. The increase in secreted biologically active VEGF protein from cells exposed to hypoxia is partly because of an increased transcription rate, mediated by binding of hypoxia-inducible factor-1 (HIF1) to a hypoxia responsive element in the 5'-flanking region of the VEGF gene. bHLH-PAS transcription factor that interacts with the Ah receptor nuclear translocator (Arnt), and its predicted amino acid sequence, exhibits significant similarity to the hypoxia-inducible factor 1alpha (HIF1a) product. HLF mRNA expression is closely correlated with that of VEGF mRNA. The high expression level of HLF mRNA in the O2 delivery system of developing embryos and adult organs suggests that in a normoxic state, HLF regulates gene expression of VEGF, various glycolytic enzymes, and others driven by the HRE sequence, and may be involved in development of blood vessels and the tubular system of lung. VEGF expression is dramatically induced by hypoxia due in large part to an increase in the stability of its mRNA. HuR binds with high affinity and specificity to the VRS element that regulates VEGF mRNA stability by hypoxia. In addition, an internal ribosome entry site (IRES) ensures efficient translation of VEGF mRNA even under hypoxia. The VHL tumor suppressor (von Hippel-Lindau) regulates also VEGF expression at a post-transcriptional level. The secreted VEGF is a major angiogenic factor that regulates multiple endothelial cell functions, including mitogenesis. Cellular and circulating levels of VEGF are elevated in hematologic malignancies and are adversely associated with prognosis. Angiogenesis is a very complex, tightly regulated, multistep process, the targeting of which may well prove useful in the creation of novel therapeutic agents. Current approaches being investigated include the inhibition of angiogenesis stimulants (e.g., VEGF), or their receptors, blockade of endothelial cell activation, inhibition of matrix metalloproteinases, and inhibition of tumor vasculature. Preclinical, phase I, and phase II studies of both monoclonal antibodies to VEGF and blockers of the VEGF receptor tyrosine kinase pathway indicate that these agents are safe and offer potential clinical utility in patients with hematologic malignancies. (BioCarta)
Bioreductive Agent definition: Antitumor agents that are activated by biological reduction and have selective efficacy against hypoxic solid tumors. (NCI)
Hypoxia-Inducible Factor Pathway definition: Hypoxia (or low O2 levels) affects various pathologies. First, tissue ischemia, a variation in O2 tension caused by hypoxia/reoxygenation, can lead to endothelial cell changes. For example, long periods of ischemia result in endothelial changes, such as vascular leakage, resulting in varicose veins. In more severe situations, ischemia can lead to myocardial or cerebral infarction and retinal vessel occlusion. Of interest, HIF-1 is stabilized prior to induction of vascular endothelial growth factor (VEGF) expression during acute ischemia in the human heart. Second, pulmonary hypertension associated with chronic respiratory disorders results from persistent vasoconstriction and vascular remodeling. Third, hypoxic gradients created in enlarging solid tumors trigger expression of genes containing hypoxia response elements (HREs) such as those involved in angiogenesis. This allows subsequent delivery of O2, nutrients, and further tumor growth. Vascular remodeling is an important component to tumorigenesis; without proper blood supply, delivery of oxygen may occur by diffusion, but becomes inefficient in tumors greater than 1 mm in diameter. Short-term hypoxia can also elevate platelet numbers, while prolonged exposure may cause some degree of thrombocytopenia in response to increased levels of erythropoietin (EPO). Another disorder involving inadequate responses to hypoxia is preeclampsia, a pathology of pregnancy thought to be caused by improper differentiation of placental trophoblast cells due to poorly controlled O2 tension or improper hypoxia-inducible factor (HIF)-mediated responses. The primary molecular mechanism of gene activation during hypoxia is through HIF-1. Several genes involved in cellular differentiation are directly or indirectly regulated by hypoxia. These include EPO, LDH-A, ET-1, transferrin, transferrin receptor, VEGF, Flk-1, Flt-1, platelet-derived growth factor-beta (PDGF-b), basic fibroblast growth factor (bFGF), and others genes affecting glycolysis. HIF-1 is a member of the basic helix-loop-helix (bHLH)-PAS family of transcription factors known to induce gene expression by binding to a 50-bp HRE containing a core 5'-ACGTG-3' sequence. bHLH-PAS proteins heterodimerize to form transcription complexes that regulate O2 homeostasis, circadian rhythms, neurogenesis, and toxin metabolism. Three bHLH-PAS proteins in vertebrates respond to hypoxia: HIF-1, EPAS (HIF-2), and HIF-3. These dimerize with ARNT (aryl hydrocarbon receptor nuclear translocator protein), ARNT-2, or ARNT-3. HIF-1 is ubiquitinated and subsequently degraded in less than 5 minutes under normoxic conditions. Although several candidate O2-sensing molecules have emerged in the literature, the molecular basis of how cells sense O2 levels is poorly characterized. pVHL, the protein product of a tumor-suppressor gene responsible for von Hippel Lindau disease, is implicated in this O2-sensing system by its association with HIF-1, targeting it for ubiquitin-mediated degradation. Similarly, F-box-containing proteins recognize substrates of the ubiquitin ligases, targeting them for phosphorylation-dependent ubiquitination and proteosomal degradation. In addition to F-boxes, most of these proteins also contain a WD40 or a leucine-rich repeat (LLR) domain that presumably functions as a Ser/Thr binding module. A second family of proteins assisting the ubiquitin ligases share a region designated SOCS-box (originally from the suppressor of cytokine signaling proteins SOCS). Under low O2 (<5% O2) HIF-1 is stabilized leading to the formation of a functional transcription factor complex with ARNT. This complex is the master regulator of O2 homeostasis and induces a network of genes involved in angiogenesis, erythropoiesis, and glucose metabolism. (BioCarta)
Hypoxia-Responsive Elements definition: DNA sequences in a gene's promoter region that mediate expression during hypoxia. Since unlike normal tissues, solid tumors frequently have regions of hypoxia, suicide genes controlled by hypoxia-responsive elements may provide a means for cancer-specific gene therapy.
Hypoxia Pathway definition: Hypoxic stress, like DNA damage, induces p53 protein accumulation and p53-dependent apoptosis in oncogenically transformed cells. Unlike DNA damage, hypoxia does not induce p53-dependent cell cycle arrest, suggesting that p53 activity is differentially regulated by these two stresses. Hypoxia induces p53 protein accumulation, but in contrast to DNA damage, hypoxia fails to induce endogenous downstream p53 effector mRNAs and proteins, such as p21, Bax, CIP1, WAF1, etc. Hypoxia does not inhibit the induction of p53 target genes by ionizing radiation, indicating that p53-dependent transactivation requires a DNA damage-inducible signal that is lacking under hypoxic treatment alone. The phosphatidylinositol 3-OH-kinase-Akt pathway inhibits p53-mediated transcription and apoptosis. Mdm2, a ubiquitin ligase for p53, plays a central role in regulation of the stability of p53 and serves as a good substrate for Akt. Mdm-2 targets the p53 tumor suppressor for ubiquitin-dependent degradation by the proteasome, but, in addition, the p53 transcription factor induces Mdm-2, thus, establishing a feedback loop. Hypoxia or DNA damage by abrogating binding of HIF-1 with VHL and p53 with Mdm-2, respectively, leads to stabilization and accumulation of transcriptionally active HIF-1 and p53. At the molecular level, DNA damage induces the interaction of p53 with the transcriptional activator p300 as well as with the transcriptional corepressor mSin3A. In contrast, hypoxia primarily induces an interaction of p53 with mSin3A, but not with p300. (BioCarta)
Hypoxia, Brain definition: A reduction in brain oxygen supply due to ANOXEMIA (a reduced amount of oxygen being carried in the blood by HEMOGLOBIN), or to a restriction of the blood supply to the brain, or both. Severe hypoxia is referred to as anoxia, and is a relatively common cause of injury to the central nervous system. Prolonged brain anoxia may lead to BRAIN DEATH or a PERSISTENT VEGETATIVE STATE. Histologically, this condition is characterized by neuronal loss which is most prominent in the HIPPOCAMPUS; GLOBUS PALLIDUS; CEREBELLUM; and inferior olives.
Hypoxia Inducible Factor 1-Alpha PX-478 definition: An orally active small molecule with potential antineoplastic activity. Although its mechanism of action has yet to be fully elucidated, HIF1-alpha inhibitor PX-478 appears to inhibit hypoxia-inducible factor 1-alpha (HIF1A) expression, which may result in decreased expression of HIF1A downstream target genes important to tumor growth and survival, a reduction in tumor cell proliferation, and the induction of tumor cell apoptosis. The inhibitory effect of this agent is independent of the tumor suppressor genes VHL and p53 and may be related to derangements in glucose uptake and metabolism due to inhibition of glucose transporter-1 (Glut-1).
Grade 2 Hypoxia definition: Decreased O(2) saturation with exercise (e.g., pulse oximeter <88%); intermittent supplemental oxygen
Grade 3 Hypoxia definition: Decreased O(2) saturation at rest; continuous oxygen indicated
Grade 4 Hypoxia definition: Life-threatening; intubation or ventilation indicated
Grade 5 Hypoxia definition: Death
Hypoxia-Activated Prodrug TH-302 definition: A hypoxia-activated prodrug consisting of a 2-nitroimidazole phosphoramidate conjugate with potential antineoplastic activity. The 2-nitroimidazole moiety of hypoxia-activated prodrug TH-302 acts as a hypoxic trigger, releasing the DNA-alkylating dibromo isophosphoramide mustard moiety within hypoxic regions of tumors. Normoxic tissues may be spared due to the hypoxia-specific activity of this agent, potentially reducing systemic toxicity.
detection of hypoxia definition: The series of events in which a stimulus indicating lowered oxygen tension is received by a cell and converted into a molecular signal. Hypoxia, defined as a decline in O2 levels below normoxic levels of 20.8 - 20.95%, results in metabolic adaptation at both the cellular and organismal level. [GOC:mah]
hypoxia definition: [1] Medizin: die Hypoxie: Sauerstoffmangel im Gewebe
anaemic hypoxia definition: [1] britisch, Medizin: die Anämiehypoxie
anemic hypoxia definition: [1] amerikanisch, Medizin: die Anämiehypoxie
diffusion hypoxia definition: [1] Medizin: die Diffusionshypoxie
hypoxia definition: Hypoxie.
 
 
frFrench
hypoxie definition: Phénomène qui se produit en milieu aquatique quand la concentration de l'oxygène dissous est réduite à un point critique pour les organismes vivants dans ce milieu.
hypoxie definition: Oxygénation insuffisante des tissus.