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

Autor: Catalin E. Doneanu, Régis F. Moreau, Tory M. Hagen, Shi Hua D. Heath, J. Gordon Lindsay
Rok vydání: 2003
Předmět:
Male
Aging
Swine
Physiology
Clinical Biochemistry
Ketoglutarate dehydrogenase
Administration
Oral
Gene Expression
Biochemistry
Mitochondria
Heart
chemistry.chemical_compound
Enzyme Inhibitors
Creatine Kinase
General Environmental Science
chemistry.chemical_classification
Thioctic Acid
biology
Chemistry
Age Factors
Cross-Linking Reagents
Electrophoresis
Polyacrylamide Gel
Polyunsaturated fatty acid
Spectrometry
Mass
Electrospray Ionization
medicine.medical_specialty
Blotting
Western
Molecular Sequence Data
Catalysis
4-Hydroxynonenal
Age related
Internal medicine
medicine
Animals
Ketoglutarate Dehydrogenase Complex
Amino Acid Sequence
Molecular Biology
Mitochondrial protein
Serum Albumin
Dihydrolipoamide Dehydrogenase
Aldehydes
Myocardium
Cell Biology
Rat heart
Rats
Inbred F344
In vitro
Enzyme assay
Rats
Kinetics
Endocrinology
biology.protein
General Earth and Planetary Sciences
Acyltransferases
Zdroj: Antioxidants & Redox Signaling. 5:517-527
ISSN: 1557-7716
1523-0864
Popis: 4-hydroxynonenal (HNE), a product of omega-6 polyunsaturated fatty acid peroxidation, impairs mitochondrial respiration in vitro by adducting the alpha-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 (por =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 (por =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 (por =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 alpha-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.
Databáze: OpenAIRE
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