The effect of age and calorie restriction on HIF-1-responsive genes in aged liver |
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Authors: | Min Ju Kang Hyon Jeen Kim Hyung Keun Kim Ji Young Lee Dae Hyun Kim Kyung Jin Jung Kyu Won Kim Hyung Suck Baik Mie Ae Yoo Byung Pal Yu Hae Young Chung |
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Institution: | (1) College of Pharmacy, Aging Tissue Bank, Pusan National University, Busan, 609-735, Korea;(2) Genetic Engineering Research Institute, Pusan National University, Busan, 609-735, Korea;(3) Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Korea;(4) Department of Physiology, The University of Texas Health Science Center, San Antonio, TX, USA |
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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-1 , 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.Min Ju Kang and Hyon Jeen Kim Contributed equally to this work |
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Keywords: | aging CR EPO HIF-1 HO-1 iNOS VEGF |
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