title: The effect of age and calorie restriction on HIF-1-responsive genes in aged liver.
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.
authors.affiliation: College of Pharmacy, Aging Tissue Bank, Pusan National University, Busan, Korea.
authors.forename: Min Ju
authors.initials: MJ
authors.lastname: Kang
authors.forename: Hyon Jeen
authors.initials: HJ
authors.lastname: Kim
authors.forename: Hyung Keun
authors.initials: HK
authors.lastname: Kim
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Dae Hyun
authors.initials: DH
authors.lastname: Kim
authors.forename: Kyung Jin
authors.initials: KJ
authors.lastname: Jung
authors.forename: Kyu Won
authors.initials: KW
authors.lastname: Kim
authors.forename: Hyung Suck
authors.initials: HS
authors.lastname: Baik
authors.forename: Mie Ae
authors.initials: MA
authors.lastname: Yoo
authors.forename: Byung Pal
authors.initials: BP
authors.lastname: Yu
authors.forename: Hae Young
authors.initials: HY
authors.lastname: Chung
mesh_terms: D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000378:metabolism; D031204:Caloric Restriction; D004268:DNA-Binding Proteins / Q000378:metabolism; D004921:Erythropoietin / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D009566:Nitrates / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D015533:Transcriptional Activation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: C497396:ARNT protein, human; D004268:DNA-Binding Proteins; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009566:Nitrates; D009573:Nitrites; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D004921:Erythropoietin; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat