Age-dependent increase of heme oxygenase-1 gene expression in the liver mediated by NFκB

Yan Lavrovsky, Chung S. Song, Bandana Chatterjee, Arun K. Roy

Research output: Contribution to journalArticle

64 Scopus citations

Abstract

Heme, the iron-porphyrin coordination complex, released from the degradation of hemoproteins, is a strong prooxidant. It is enzymatically degraded by heme oxygenase to free iron, carbon monoxide and biliverdin. Biliverdin and its reduced metabolite bilirubin are two potent physiological antioxidants. Here we show a progressive increase of steady-state levels of the mRNA encoding the inducible isoform of this enzyme (heme oxygenase-1) in the rat liver during aging. We had previously reported that aging is associated with increased activation of the nuclear factor κB (NFκB). We now provide evidence to establish that overexpression of NFκB in transfected liver-derived HepG2 cells can cause a marked induction of the endogenous heme oxygenase-1 (HO-1) mRNA and activation of the cotransfected HO-1 gene promoter. Taken together, these results support the conclusion that enhanced oxidative stress during aging is accompanied by compensatory induction of the antioxidant enzyme HO-1 through activation of the NFκB pathway. Copyright (C) 2000 Elsevier Science Ireland Ltd.

Original languageEnglish (US)
Pages (from-to)49-60
Number of pages12
JournalMechanisms of Ageing and Development
Volume114
Issue number1
DOIs
StatePublished - Feb 22 2000

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Keywords

  • Aging
  • Heme oxygenase-1
  • Nuclear factor κB
  • Reactive oxidative species
  • Transcriptional regulation

ASJC Scopus subject areas

  • Aging
  • Developmental Biology

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