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The effect of age and calorie restriction on HIF-1-responsive genes in aged liver

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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-1α, 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.

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Abbreviations

EPO:

erythropoietin

HIF-1:

hypoxia inducible factor 1

HO-1:

heme oxygenase-1

iNOS:

inducible nitric oxide synthase

NO:

nitric oxide

Nox:

nitrate plus nitrite

ROS:

reactive oxygen species

VEGF:

vascular endothelial growth factor

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Authors and Affiliations

  1. College of Pharmacy, Aging Tissue Bank, Pusan National University, Busan, 609-735, Korea

    Min Ju Kang, Hyon Jeen Kim, Dae Hyun Kim, Kyung Jin Jung & Hae Young Chung

  2. Genetic Engineering Research Institute, Pusan National University, Busan, 609-735, Korea

    Hyung Keun Kim, Ji Young Lee, Hyung Suck Baik, Mie Ae Yoo & Hae Young Chung

  3. Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Korea

    Kyu Won Kim

  4. Department of Physiology, The University of Texas Health Science Center, San Antonio, TX, USA

    Byung Pal Yu

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  1. Min Ju Kang
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Correspondence to Hae Young Chung.

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Min Ju Kang and Hyon Jeen Kim Contributed equally to this work

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Kang, M.J., Kim, H.J., Kim, H.K. et al. The effect of age and calorie restriction on HIF-1-responsive genes in aged liver. Biogerontology 6, 27–37 (2005). https://doi.org/10.1007/s10522-004-7381-z

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