Age-Related Increase in 4-Hydroxynonenal Adduction to Rat Heart α-Ketoglutarate Dehydrogenase Does Not Cause Loss of Its Catalytic Activity

Régis Moreau, Shi Hua D. Heath, Catalin E. Doneanu, J. Gordon Lindsay, Tory M. Hagen

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

4-Hydroxynonenal (HNE), a product of ω-6 polyunsaturated fatty acid peroxidation, impairs mitochondrial respiration in vitro by adducting the α-ketoglutarate dehydrogenase complex (KGDC) and inhibiting its activity. The present study seeks to define whether aging increases HNE adduction to rat heart KGDC, and whether such adduction impacts KGDC activity. We found that hearts from old rats exhibit significantly (p ≤ 0.01) higher HNE-modified mitochondrial proteins when compared with those from young rats. Among these proteins, dihydrolipoamide succinyltransferase, the E2k component of KGDC, was most markedly modified (p ≤ 0.01) by HNE with age. As opposed to that seen in vitro, no significant change in electrophoretic mobility or impairment in enzyme activity was observed. On the contrary, KGDC activity increased onefold (p ≤ 0.01) in old rats, suggesting that the aging myocardium is not affected by HNE adduction or compensates for such damage. Further analysis revealed that heightened KGDC activity was not due to increased protein content or gene expression, but correlates with a lower Km for α-ketoglutarate. Thus, contrary to that observed in vitro, the measurement of HNE-KGDC adduct in rat heart is more relevant as a marker of age-related protein oxidation than a factor of mitochondrial dysfunction.

Original languageEnglish (US)
Pages (from-to)517-527
Number of pages11
JournalAntioxidants and Redox Signaling
Volume5
Issue number5
DOIs
StatePublished - Oct 2003

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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