Abstract
Hypoxia inducible factor-1 (HIF-1) regulates transactivation of several genes in response to hypoxia condition. We explore hepatic HIF-1 responsive gene regulation during aging and the age-related changes of the HIF-1 related gene activation in young and old rats. Results indicate that the aging process induces the activation of HIF-1alpha, which is accompanied by increased HIF-1 DNA binding. This increased binding activity is accompanied by the increase of HIF-1-dependent genes, heme oxygenase-1 (HO-1), vascular endothelial growth factor (VEGF), erythropoietin (EPO), and inducible nitric oxide synthase (iNOS), which all showed remarkable up-regulation during aging process. In contrast, the increased HIF-1 related gene expression was effectively blunted by the anti-oxidative action of calorie restriction in aged rat liver. We propose that age-related HIF-1 binding activity may well be influenced by the increased pro-oxidative conditions of aged animals, which up-regulate HIF-1-dependent gene expression.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Aging / genetics
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Aging / metabolism*
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Animals
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Aryl Hydrocarbon Receptor Nuclear Translocator / metabolism
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Caloric Restriction*
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DNA-Binding Proteins / metabolism
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Erythropoietin / genetics
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Erythropoietin / metabolism
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Gene Expression Regulation*
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Heme Oxygenase (Decyclizing) / genetics
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Heme Oxygenase (Decyclizing) / metabolism
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Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
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Liver / metabolism*
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Male
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Nitrates / metabolism
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Nitric Oxide Synthase Type II / genetics
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Nitric Oxide Synthase Type II / metabolism
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Nitrites / metabolism
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RNA, Messenger / metabolism
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Rats
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Rats, Inbred F344
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Transcriptional Activation
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Vascular Endothelial Growth Factor A / genetics
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Vascular Endothelial Growth Factor A / metabolism
Substances
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ARNT protein, human
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DNA-Binding Proteins
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Hif1a protein, rat
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Hypoxia-Inducible Factor 1, alpha Subunit
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Nitrates
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Nitrites
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RNA, Messenger
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Vascular Endothelial Growth Factor A
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vascular endothelial growth factor A, rat
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Erythropoietin
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Aryl Hydrocarbon Receptor Nuclear Translocator
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Nitric Oxide Synthase Type II
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Nos2 protein, rat
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Heme Oxygenase (Decyclizing)
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Hmox1 protein, rat