Journal ArticleDOI
Role of hypoxia-inducible factor-1 in hypoxia-induced ischemic tolerance in neonatal rat brain
Marcelle Bergeron,Jeffrey M. Gidday,Aimee Y. Yu,Gregg L. Semenza,Donna M. Ferriero,Frank R. Sharp,Frank R. Sharp +6 more
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TLDR
HIF‐1 activation could contribute to protective brain preconditioning, which could be used in high‐risk deliveries and other clinical situations.Abstract:
Hypoxia-inducible factor-1 (HIF-1) is a heterodimer composed of HIF-1alpha and HIF-1beta protein subunits. This transcription factor is essential for the activation of hypoxia-inducible genes like erythropoietin, some glucose transporters, the glycolytic enzymes, and vascular endothelial growth factor. Because HIF-1 activation may promote cell survival in hypoxic tissues, we studied the effect of hypoxic preconditioning on HIF-1 expression in neonatal rat brain. Hypoxic preconditioning (8% O2 for 3 hours), a treatment known to protect the newborn rat brain against hypoxic-ischemic injury, markedly increased HIF-1alpha and HIF-1beta expression. To support the role of HIF-1 in protective preconditioning, we also studied the effect of two other known HIF-1 inducers, cobalt chloride (CoCl2) and desferrioxamine (DFX), on HIF-1 expression and neuroprotection in newborn brain. HIF-1alpha and HIF-1beta protein levels were markedly increased after intraperitoneal injection of CoCl2 (60 mg/kg) and moderately increased after intraperitoneal injection of DFX (200 mg/kg) 1 to 3 hours after the injections. Preconditioning with CoCl2 or DFX 24 hours before hypoxia-ischemia afforded 75 and 56% brain protection, respectively, compared with that in vehicle-injected littermate controls. Thus, HIF-1 activation could contribute to protective brain preconditioning, which could be used in high-risk deliveries and other clinical situations.read more
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Hypoxia-inducible factor 1: Oxygen homeostasis and disease pathophysiology
TL;DR: Modulation of HIF-1 activity by genetic or pharmacological means could provide a novel therapeutic approach to these common causes of mortality.
Journal ArticleDOI
HIF-1 and human disease: one highly involved factor
TL;DR: The regulation of VEGF expression illustrates how reduced O2 availability (hypoxia) can elicit physiological responses via multiple molecular mechanisms, and the molecular mechanisms of sensing and signal transduction by which changes in O2 concentration result in changes in HIF-1 activity are poorly understood.
Journal ArticleDOI
Oxygen Sensing, Homeostasis, and Disease
TL;DR: This review summarizes advances in the understanding of how cells sense and respond to changes in oxygen availability and the physiologic or pathologic consequences of these responses in the context of chronic diseases.
Journal ArticleDOI
Hypoxia-inducible Factor 1 Activation by Aerobic Glycolysis Implicates the Warburg Effect in Carcinogenesis
TL;DR: Findings support a novel role for pyruvate in metabolic signaling and suggest a mechanism by which high rates of aerobic glycolysis can promote the malignant transformation and survival of cancer cells.
Journal ArticleDOI
Cerebral preconditioning and ischaemic tolerance
TL;DR: Current understanding of how 'preconditioning' stimuli trigger a cerebroprotective state known as cerebral 'ischaemic tolerance' is summarized.
References
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Journal ArticleDOI
Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension
TL;DR: Hypoxia-inducible factor 1 (HIF-1) is found in mammalian cells cultured under reduced O2 tension and is necessary for transcriptional activation mediated by the erythropoietin gene enhancer in hypoxic cells.
Journal ArticleDOI
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.
Gregg L. Semenza,Guang L. Wang +1 more
TL;DR: A functionally tripartite, 50-nt hypoxia-inducible enhancer which binds several nuclear factors, one of which is induced by Hypoxia via de novo protein synthesis.
Journal ArticleDOI
Cellular and developmental control of O2 homeostasis by hypoxia-inducible factor 1α
Narayan V. Iyer,Lori E. Kotch,Faton Agani,Sandra W. Leung,Erik Laughner,Roland H. Wenger,Max Gassmann,John D. Gearhart,Ann M. Lawler,Aimee Y. Yu,Gregg L. Semenza +10 more
TL;DR: It is demonstrated that HIF-1alpha is a master regulator of cellular and developmental O2 homeostasis in Hif1a-/- embryos that manifested neural tube defects, cardiovascular malformations, and marked cell death within the cephalic mesenchyme.
Journal ArticleDOI
Role of HIF-1alpha in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis.
Peter Carmeliet,Yuval Dor,Jean-Marc Herbert,Dai Fukumura,Koen Brusselmans,Mieke Dewerchin,Michal Neeman,Françoise Bono,Rinat Abramovitch,Patrick H. Maxwell,Cameron J. Koch,Peter J. Ratcliffe,Lieve Moons,Rakesh K. Jain,Desire Collen,Eli Keshert +15 more
TL;DR: It is shown that hypoxia and hypoglycaemia reduce proliferation and increase apoptosis in wild-type (Hif-1α+/+) embryonic stem (ES) cells, but not in ES cells with inactivated HIF-1 α genes (HIF- 1α−/−), suggesting that there are at least two different adaptive responses to being deprived of oxygen and nutrients.
Journal ArticleDOI
Regulation of hypoxia-inducible factor 1α is mediated by an O2-dependent degradation domain via the ubiquitin-proteasome pathway
TL;DR: The identification of an oxygen-dependent degradation (ODD) domain within HIF-1alpha that controls its degradation by the ubiquitin-proteasome pathway is reported and may provide a means of controlling gene expression by changes in oxygen tension.