Genomes and Genes
Gene Symbol: Hif1a
Description: hypoxia inducible factor 1 alpha subunit
Alias: MOP1, hypoxia-inducible factor 1-alpha, HIF-1-alpha, HIF1-alpha, hypoxia-inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)
- Hui A, Bauer A, Striet J, Schnell P, Czyzyk Krzeska M. Calcium signaling stimulates translation of HIF-alpha during hypoxia. FASEB J. 2006;20:466-75 pubmed
- Guo S, Bragina O, Xu Y, Cao Z, Chen H, Zhou B, et al. Glucose up-regulates HIF-1 alpha expression in primary cortical neurons in response to hypoxia through maintaining cellular redox status. J Neurochem. 2008;105:1849-60 pubmed publisher..The results imply that hypoxia only may not be sufficient to stabilize HIF-1alpha and that a reducing environment is required to stabilize HIF-1alpha in neurons exposed to hypoxia. ..
- Caretti A, Morel S, Milano G, Fantacci M, Bianciardi P, Ronchi R, et al. Heart HIF-1alpha and MAP kinases during hypoxia: are they associated in vivo?. Exp Biol Med (Maywood). 2007;232:887-94 pubmed..In conclusion, although very sensitive to the reoxygenation, HIF-1alpha is overexpressed in vivo in the hypoxic myocardium, and its acute induction by hypoxia is correlated with that of p38. ..
- Cheng J, Kang X, Zhang S, Yeh E. SUMO-specific protease 1 is essential for stabilization of HIF1alpha during hypoxia. Cell. 2007;131:584-95 pubmed..These results show that SENP1 plays a key role in the regulation of the hypoxic response through regulation of HIF1alpha stability and that SUMOylation can serve as a direct signal for ubiquitin-dependent degradation. ..
- Ohtomo S, Nangaku M, Izuhara Y, Takizawa S, Strihou C, Miyata T. Cobalt ameliorates renal injury in an obese, hypertensive type 2 diabetes rat model. Nephrol Dial Transplant. 2008;23:1166-72 pubmed..Cobalt achieved renal protection independently of metabolic status and blood pressure. Its effect was attributed to the upregulation of HIF and HIF-regulated genes and to a mitigated advanced glycation and oxidative stress. ..
- Li S, Ran Y, Zhang D, Chen J, Li S, Zhu D. MicroRNA-138 plays a role in hypoxic pulmonary vascular remodelling by targeting Mst1. Biochem J. 2013;452:281-91 pubmed publisher..Therefore the results of the present study suggest that miR-138 appears to be a negative regulator of PASMC apoptosis, and plays an important role in HPVR (hypoxic pulmonary vascular remodelling). ..
- Zhou Y, Zheng X, Zhang G, Zong Z, Qi G. The effect of hypoxia-inducible factor 1-alpha on hypoxia-induced apoptosis in primary neonatal rat ventricular myocytes. Cardiovasc J Afr. 2010;21:37-41 pubmed..Targeting HIF-1alpha may be a new strategy for reducing the degree of hypoxia-induced apoptosis in ventricular myocytes. ..
- Baranova O, Miranda L, Pichiule P, Dragatsis I, Johnson R, Chavez J. Neuron-specific inactivation of the hypoxia inducible factor 1 alpha increases brain injury in a mouse model of transient focal cerebral ischemia. J Neurosci. 2007;27:6320-32 pubmed
- Song Y, You S, Lee Y, Chin H, Chae D, Oh Y, et al. Activation of hypoxia-inducible factor attenuates renal injury in rat remnant kidney. Nephrol Dial Transplant. 2010;25:77-85 pubmed publisher..This renoprotection was accompanied by a reduction of oxidative stress, inflammation and fibrosis. ..
- Li N, Chen L, Yi F, Xia M, Li P. Salt-sensitive hypertension induced by decoy of transcription factor hypoxia-inducible factor-1alpha in the renal medulla. Circ Res. 2008;102:1101-8 pubmed publisher..In conclusion, HIF-1alpha-mediated gene activation importantly participates in the regulation of renal medullary function and long-term arterial blood pressure...
- Keith B, Johnson R, Simon M. HIF1? and HIF2?: sibling rivalry in hypoxic tumour growth and progression. Nat Rev Cancer. 2011;12:9-22 pubmed publisher..As HIF inhibitors are currently undergoing clinical evaluation as cancer therapeutics, a more thorough understanding of the unique roles performed by HIF1? and HIF2? in human neoplasia is warranted. ..
- Higgins D, Kimura K, Bernhardt W, Shrimanker N, Akai Y, Hohenstein B, et al. Hypoxia promotes fibrogenesis in vivo via HIF-1 stimulation of epithelial-to-mesenchymal transition. J Clin Invest. 2007;117:3810-20 pubmed
- Bernhardt W, Campean V, Kany S, Jurgensen J, Weidemann A, Warnecke C, et al. Preconditional activation of hypoxia-inducible factors ameliorates ischemic acute renal failure. J Am Soc Nephrol. 2006;17:1970-8 pubmed..Inhibiting the activity of HIF hydroxylases therefore seems to have considerable clinical perspectives. ..
- Yuan G, Nanduri J, Khan S, Semenza G, Prabhakar N. Induction of HIF-1alpha expression by intermittent hypoxia: involvement of NADPH oxidase, Ca2+ signaling, prolyl hydroxylases, and mTOR. J Cell Physiol. 2008;217:674-85 pubmed publisher..Rapamycin or cycloheximide, blocked increased HIF-1alpha levels during re-oxygenation indicating that mTOR-dependent protein synthesis is required for the persistent elevation of HIF-1alpha levels during re-oxygenation. ..
- Bianciardi P, Fantacci M, Caretti A, Ronchi R, Milano G, Morel S, et al. Chronic in vivo hypoxia in various organs: hypoxia-inducible factor-1alpha and apoptosis. Biochem Biophys Res Commun. 2006;342:875-80 pubmed..We conclude that the HIF-1alpha response to chronic hypoxia can be a sustained phenomenon, but not in all organs, and that apoptosis responds differently from HIF-1alpha. ..
- Kazi A, Jones J, Koos R. Chromatin immunoprecipitation analysis of gene expression in the rat uterus in vivo: estrogen-induced recruitment of both estrogen receptor alpha and hypoxia-inducible factor 1 to the vascular endothelial growth factor promoter. Mol Endocrinol. 2005;19:2006-19 pubmed..In contrast to the uterus, HEC1A cells cultured in 95% air-5% CO2 (and therefore 20% O2) contained no HIF-1alpha, consistent with the inability of E2 to stimulate the expression of VEGF by these and other cell types in vitro. ..
- Zhang L, Qu Y, Yang C, Tang J, Zhang X, Mao M, et al. Signaling pathway involved in hypoxia-inducible factor-1alpha regulation in hypoxic-ischemic cortical neurons in vitro. Neurosci Lett. 2009;461:1-6 pubmed publisher..Collectively, our findings suggested that PI3K/Akt signaling pathway might be involved in HIF-1alpha regulation after OGD in cultured cortical neurons. ..
- Heinis M, Simon M, Ilc K, Mazure N, Pouyssegur J, Scharfmann R, et al. Oxygen tension regulates pancreatic beta-cell differentiation through hypoxia-inducible factor 1alpha. Diabetes. 2010;59:662-9 pubmed publisher..These data demonstrate that beta-cell differentiation is controlled by pO2 through HIF1alpha. Modifying pO2 should now be tested in protocols aiming to differentiate beta-cells from embryonic stem cells. ..
- Conde E, Alegre L, Blanco Sánchez I, Sáenz Morales D, Aguado Fraile E, Ponte B, et al. Hypoxia inducible factor 1-alpha (HIF-1 alpha) is induced during reperfusion after renal ischemia and is critical for proximal tubule cell survival. PLoS ONE. 2012;7:e33258 pubmed publisher..In summary, using experimental models and human biopsies, we identified a novel HIF-1 ? induction during reperfusion with a potential critical role in renal transplant. ..
- Sanchez Lopez E, López A, Esteban V, Yagüe S, Egido J, Ruiz Ortega M, et al. Angiotensin II regulates vascular endothelial growth factor via hypoxia-inducible factor-1alpha induction and redox mechanisms in the kidney. Antioxid Redox Signal. 2005;7:1275-84 pubmed..In summary, these data show that AngII in vivo and in vitro up-regulates renal VEGF expression by a mechanism that involves HIF-1 activation and oxidative stress. ..
- Teng M, Dang Y, Zhang J, Zhang Q, Fang Y, Ren J, et al. Microtubular stability affects cardiomyocyte glycolysis by HIF-1alpha expression and endonuclear aggregation during early stages of hypoxia. Am J Physiol Heart Circ Physiol. 2010;298:H1919-31 pubmed publisher..These findings provide potential therapeutic targets for ameliorating cell energy metabolism during early myocardial hypoxia. ..
- Belaidi E, Joyeux Faure M, Ribuot C, Launois S, Levy P, Godin Ribuot D. Major role for hypoxia inducible factor-1 and the endothelin system in promoting myocardial infarction and hypertension in an animal model of obstructive sleep apnea. J Am Coll Cardiol. 2009;53:1309-17 pubmed publisher..Furthermore, the beneficial effects of bosentan suggest exploring ET antagonists as possible therapeutic tools in OSA. ..
- Michaud M, Robitaille G, Gratton J, Richard D. Sphingosine-1-phosphate: a novel nonhypoxic activator of hypoxia-inducible factor-1 in vascular cells. Arterioscler Thromb Vasc Biol. 2009;29:902-8 pubmed publisher..Our results identify S1P as a novel and potent nonhypoxic activator of HIF-1. We believe that understanding the role played by HIF-1 in S1P gene regulation will have a strong impact on different aspects of vascular biology. ..
- Schipani E, Ryan H, Didrickson S, Kobayashi T, Knight M, Johnson R. Hypoxia in cartilage: HIF-1alpha is essential for chondrocyte growth arrest and survival. Genes Dev. 2001;15:2865-76 pubmed
- Powell J, Elshtein R, Forest D, Palladino M. Stimulation of hypoxia-inducible factor-1 alpha (HIF-1alpha) protein in the adult rat testis following ischemic injury occurs without an increase in HIF-1alpha messenger RNA expression. Biol Reprod. 2002;67:995-1002 pubmed..HIF-1alpha protein was also elevated by experimental torsion and reperfusion compared with normoxic controls. These results support the hypothesis that HIF-1 may play a role in the cellular response to hypoxia in the ischemic testis...
- Peters C, Morris C, Mapp P, Blake D, Lewis C, Winrow V. The transcription factors hypoxia-inducible factor 1alpha and Ets-1 colocalize in the hypoxic synovium of inflamed joints in adjuvant-induced arthritis. Arthritis Rheum. 2004;50:291-6 pubmed..The colocalization of Ets-1 and HIF-1alpha in these hypoxic areas suggests that hypoxia may induce Ets-1 and HIF-1alpha expression during joint inflammation. ..
- Giatromanolaki A, Sivridis E, Maltezos E, Athanassou N, Papazoglou D, Gatter K, et al. Upregulated hypoxia inducible factor-1alpha and -2alpha pathway in rheumatoid arthritis and osteoarthritis. Arthritis Res Ther. 2003;5:R193-201 pubmed..The activation of the HIF-alpha pathway occurs in both RA and OA, although for unrelated reasons. ..
- Yu A, Shimoda L, Iyer N, Huso D, Sun X, McWilliams R, et al. Impaired physiological responses to chronic hypoxia in mice partially deficient for hypoxia-inducible factor 1alpha. J Clin Invest. 1999;103:691-6 pubmed..Expression of the HIF-1alpha subunit increases exponentially as O2 concentration is decreased. Hif1a-/- mouse embryos with complete deficiency of HIF-1alpha due to homozygosity for a null allele at the Hif1a locus ..
- Forsythe J, Jiang B, Iyer N, Agani F, Leung S, Koos R, et al. Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1. Mol Cell Biol. 1996;16:4604-13 pubmed..VEGF mRNA was not induced by hypoxia in mutant cells that do not express the HIF-1beta (ARNT) subunit. These findings implicate HIF-1 in the activation of VEGF transcription in hypoxic cells. ..
- Ema M, Taya S, Yokotani N, Sogawa K, Matsuda Y, Fujii Kuriyama Y. A novel bHLH-PAS factor with close sequence similarity to hypoxia-inducible factor 1alpha regulates the VEGF expression and is potentially involved in lung and vascular development. Proc Natl Acad Sci U S A. 1997;94:4273-8 pubmed
- Compernolle V, Brusselmans K, Franco D, Moorman A, Dewerchin M, Collen D, et al. Cardia bifida, defective heart development and abnormal neural crest migration in embryos lacking hypoxia-inducible factor-1alpha. Cardiovasc Res. 2003;60:569-79 pubmed..HIF-1alpha is essential for proper cardiac development by modulating both neural crest migration and ventricle formation. ..
- Chavez J, Lamanna J. Activation of hypoxia-inducible factor-1 in the rat cerebral cortex after transient global ischemia: potential role of insulin-like growth factor-1. J Neurosci. 2002;22:8922-31 pubmed..Our study suggest that activation of HIF-1 might be part of the mechanism by which IGF-1 promotes cell survival after cerebral ischemia. ..
- Gorlach A, Berchner Pfannschmidt U, Wotzlaw C, Cool R, Fandrey J, Acker H, et al. Reactive oxygen species modulate HIF-1 mediated PAI-1 expression: involvement of the GTPase Rac1. Thromb Haemost. 2003;89:926-35 pubmed..In contrast, NFkappaB activation was enhanced in RacG12V-cells, but abolished by RacT17N. Thus, these findings suggest a mechanism explaining modified fibrinolysis and tissue remodeling in an oxidized environment. ..
- Matrone C, Pignataro G, Molinaro P, Irace C, Scorziello A, Di Renzo G, et al. HIF-1alpha reveals a binding activity to the promoter of iNOS gene after permanent middle cerebral artery occlusion. J Neurochem. 2004;90:368-78 pubmed..Our study suggests that the activation of HIF-1 might be involved in the mechanisms whereby iNOS promotes cell survival and/or death after cerebral ischemia. ..
- Iyer N, Kotch L, Agani F, Leung S, Laughner E, Wenger R, et al. Cellular and developmental control of O2 homeostasis by hypoxia-inducible factor 1 alpha. Genes Dev. 1998;12:149-62 pubmed..We now report that in Hif1a-/- embryonic stem cells that did not express the O2-regulated HIF-1alpha subunit, levels of mRNAs encoding glucose ..
- Kotch L, Iyer N, Laughner E, Semenza G. Defective vascularization of HIF-1alpha-null embryos is not associated with VEGF deficiency but with mesenchymal cell death. Dev Biol. 1999;209:254-67 pubmed..In Hif1a-/- knockout mice, complete deficiency of HIF-1alpha resulted in cardiac and vascular malformations and embryonic ..
- Yuan G, Nanduri J, Bhasker C, Semenza G, Prabhakar N. Ca2+/calmodulin kinase-dependent activation of hypoxia inducible factor 1 transcriptional activity in cells subjected to intermittent hypoxia. J Biol Chem. 2005;280:4321-8 pubmed..These observations suggest that IH induces HIF-1 transcriptional activity via a novel signaling pathway involving CaM kinase. ..
- 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. Mol Cell Biol. 1992;12:5447-54 pubmed..We have thus defined 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. ..
- Wang G, Jiang B, Rue E, Semenza G. Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc Natl Acad Sci U S A. 1995;92:5510-4 pubmed
- Wang Y, Luk J, Ikeda K, Man K, Chu A, Kaneda K, et al. Regulatory role of vHL/HIF-1alpha in hypoxia-induced VEGF production in hepatic stellate cells. Biochem Biophys Res Commun. 2004;317:358-62 pubmed..Inhibition of COX-2 activities would prevent vHL protein from degradation and suppress HIF-1alpha up-regulation. Thus, vHL/HIF-1alpha has a regulatory role in COX-2-mediated VEGF production in hypoxic stellate cells in injured liver. ..
- Pagé E, Robitaille G, Pouyssegur J, Richard D. Induction of hypoxia-inducible factor-1alpha by transcriptional and translational mechanisms. J Biol Chem. 2002;277:48403-9 pubmed..Elucidation of these signaling pathways that up-regulate the vascular endothelial growth factor (VEGF) could have a strong impact on different aspects of vascular biology. ..
- Yan J, Huang Y, Lu Y, Chen J, Jiang H. Repeated administration of ketamine can induce hippocampal neurodegeneration and long-term cognitive impairment via the ROS/HIF-1? pathway in developing rats. Cell Physiol Biochem. 2014;33:1715-32 pubmed publisher..Cognitive deficits were found only in the ketamine group. We suggest that ketamine-induced neurodegeneration in neonatal rats, followed by long-term cognitive deficits, might be mediated via the ROS/HIF-1? pathway. ..
- Chen Y, Doughman Y, Gu S, Jarrell A, Aota S, Cvekl A, et al. Cited2 is required for the proper formation of the hyaloid vasculature and for lens morphogenesis. Development. 2008;135:2939-48 pubmed publisher..Deletion of Hif1a (which encodes HIF-1alpha) in Cited2(-/-) lens specifically eliminated the excessive accumulation of cellular mass ..
- Charbonneau M, Harper K, Grondin F, Pelmus M, McDonald P, Dubois C. Hypoxia-inducible factor mediates hypoxic and tumor necrosis factor alpha-induced increases in tumor necrosis factor-alpha converting enzyme/ADAM17 expression by synovial cells. J Biol Chem. 2007;282:33714-24 pubmed..These findings suggest a mechanism by which TACE is increased in RA-affected joints. They also provide novel mechanistic clues on the influence of the hypoxic and inflammatory microenvironment on joint diseases. ..
- Kong C, Dai A. [Mitogen-activated protein kinase regulated hypoxia-inducible factor 1alpha in hypoxia-induced pulmonary hypertension in rats]. Zhonghua Jie He He Hu Xi Za Zhi. 2005;28:328-32 pubmed..01); p-ERK was positively correlated with HIF-1alpha mRNA and protein (tunica intima). MAPK as a signal transduction may play an important role in the development of hypoxia-induced pulmonary hypertension. ..
- Li J, Jiang G, Chen Y, Chen L, Li Z, Wang Z, et al. Altered expression of hypoxia-Inducible factor-1? participates in the epileptogenesis in animal models. Synapse. 2014;68:402-9 pubmed publisher..Our study suggests that upregulated HIF-1? may be involved in the process of epileptogenesis but not in the acute stage of epilepsy. The modulation of HIF-1? may offer a novel therapeutic target in epilepsy. ..
- Wang L, Zhang P, Wang H, Yu J, Zhang M, Han X, et al. [Intermittent hypoxia promotes the expressions of rat hippocampal neuronal hypoxia-inducible factor-1 and survivin]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2015;31:338-41 pubmed..Early IH can induce HIF-1 and survivin protein expressions in rat hippocampal CA1, and their expressions may play an important role in the regulation of neuronal apoptosis. ..
- Niu Z, Wang C, Hou Y, Yang Y, Gao H. [Expression of Stat3, HIF-1alpha and VEGF in Wilms' tumor]. Zhongguo Dang Dai Er Ke Za Zhi. 2007;9:461-4 pubmed..Stat3 may regulate the expression of HIF-1 and VEGF, so it could be an effective target for inhibiting VEGF expression and angiogenesis of Wilms' tumor. ..
- Rosenberger C, Khamaisi M, Abassi Z, Shilo V, Weksler Zangen S, Goldfarb M, et al. Adaptation to hypoxia in the diabetic rat kidney. Kidney Int. 2008;73:34-42 pubmed..Our data suggest that both regional hypoxia and hypoxia adaptation transiently occur in early stages of experimental diabetes, largely dependent on hyperglycemia or after contrast media. Tempol may augment the HIF response in diabetes. ..
- Yoon D, Pastore Y, Divoky V, Liu E, Mlodnicka A, Rainey K, et al. Hypoxia-inducible factor-1 deficiency results in dysregulated erythropoiesis signaling and iron homeostasis in mouse development. J Biol Chem. 2006;281:25703-11 pubmed..These results identify a novel role for HIF-1 in the regulation of iron homeostasis and reveal unexpected regulatory differences in Epo/EpoR signaling in yolk sac and embryonic erythropoiesis. ..
- Kadry M, Ali H. Downregulation of HIF1-?, Smad-2, AKT, and Bax gene expression in sodium nitrite-induced lung injury via some antioxidants. J Biochem Mol Toxicol. 2017;31: pubmed publisher..Interestingly the combination regimen showed the most significant effect. ..
- Bateman R, Tokunaga C, Kareco T, Dorscheid D, Walley K. Myocardial hypoxia-inducible HIF-1alpha, VEGF, and GLUT1 gene expression is associated with microvascular and ICAM-1 heterogeneity during endotoxemia. Am J Physiol Heart Circ Physiol. 2007;293:H448-56 pubmed..HIF-1alpha and GLUT1 gene induction are related to a heterogeneous ICAM-1 expression and may be cardioprotective during the onset of septic injury. ..
- Chao H, Chuang M, Liu J, Liu X, Ho L, Pan W, et al. Baicalein protects against retinal ischemia by antioxidation, antiapoptosis, downregulation of HIF-1?, VEGF, and MMP-9 and upregulation of HO-1. J Ocul Pharmacol Ther. 2013;29:539-49 pubmed publisher..Retinal ischemia-associated ocular disorders are vision threatening. This study examined whether the flavonoid baicalein is able to protect against retinal ischemia/reperfusion...
- Ferrigno A, Di Pasqua L, Bianchi A, Richelmi P, Vairetti M. Metabolic shift in liver: correlation between perfusion temperature and hypoxia inducible factor-1Î±. World J Gastroenterol. 2015;21:1108-16 pubmed publisher..16 and 3.65Â±0.06 vs 4.43Â±0.41 and 6.44Â±0.82, respectively, Ps<0.05) expression. Livers perfused at 10 and 20â€…Â°C show no sign of liver injury or anaerobiosis, in contrast to livers perfused at 30 and 37â€…Â°C. ..