Hypoxia-inducible factor 1: control of oxygen homeostasis in health and disease.
Hypoxia-inducible factor 1 (HIF-1) is a transcriptional activator that mediates changes in gene expression in response to changes in cellular oxygen concentrations. HIF-1 is a heterodimer consisting of an oxygen-regulated HIF-1 alpha subunit and a constitutively expressed HIF-1 beta subunit. In mice, complete HIF-1 alpha deficiency results in embryonic lethality at midgestation because of cardiac and vascular malformations. Analyses of animal and cell culture models as well as human tissue have provided evidence that HIF-1 plays important roles in the pathophysiology of preeclampsia, intrauterine growth retardation, hypoxia-mediated pulmonary hypertension, and cancer. HIF-1 promotes neovascularization in response to myocardial or retinal ischemia by activating transcription of the gene encoding vascular endothelial growth factor. HIF-1 may also mediate the protective response to cerebral ischemia known as late-phase preconditioning.
Semenza
G L
GL
Institute of Genetic Medicine and Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA. gsemenza@jhmi.edu
D002545:Brain Ischemia / Q000503:physiopathology; D004268:DNA-Binding Proteins / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007511:Ischemia / Q000503:physiopathology; D017202:Myocardial Ischemia / Q000503:physiopathology; D009687:Nuclear Proteins / Q000502:physiology*; D010100:Oxygen / Q000378:metabolism*; D012171:Retinal Vessels / Q000503:physiopathology; D014157:Transcription Factors
D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D014157:Transcription Factors; D010100:Oxygen