The effect of age and calorie restriction on HIF-1-responsive genes in aged liver.
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.
Kang
Min Ju
MJ
College of Pharmacy, Aging Tissue Bank, Pusan National University, Busan, Korea.
Kim
Hyon Jeen
HJ
Kim
Hyung Keun
HK
Lee
Ji Young
JY
Kim
Dae Hyun
DH
Jung
Kyung Jin
KJ
Kim
Kyu Won
KW
Baik
Hyung Suck
HS
Yoo
Mie Ae
MA
Yu
Byung Pal
BP
Chung
Hae Young
HY
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
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