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Article Dans Une Revue Biochimica et Biophysica Acta - Molecular Basis of Disease Année : 2012

Catalase, a target of glycation damage in rat liver mitochondria with aging

Résumé

Aging is characterized by progressive decline of major cell functions, associated with accumulation of altered macromolecules, particularly proteins. This deterioration parallels age-related dysfunction of mitochondria, thought to be a major determinant of this decline in cell function, since these organelles are both the main sources of reactive oxygen species and targets for their damaging effects. To investigate the link between glycation damages that accumulate with aging and the status of mitochondrial antioxidant enzymes, we identified, by mass spectrometry after two dimensional-gel electrophoresis and western blotting, advanced glycation endproduct-modified matrix proteins in rat liver mitochondria. Catalase appeared to be the only antioxidant enzyme markedly glycated in old rats. Immunogold labeling performed on isolated mitochondria confirmed the mitochondrial matrix location of this enzyme. The content of catalase protein in mitochondrial extract increased with aging whereas the catalase activity was not significantly modified, in spite of a significant increase rate of glycation. Treatment of catalase with the glycating agent fructose led to significant time-dependent inactivation of the enzyme, while methylglyoxal had no noticeable effect. Catalase was co-identified with unglycated glutathione peroxidase-1 in the mitochondrial extracts. Taken together, these results indicate that both anti-oxidant enzymes catalase and glutathione peroxidase-1 housed in liver mitochondria, exhibited a differential sensitivity to glycation; moreover, they lend support to the hypothesis that glycation damages targeting catalase with aging may severely affect its activity, suggesting a link between glycation stress and the age-related decline in antioxidant defense in the mitochondria.

Dates et versions

hal-01543994 , version 1 (21-06-2017)

Identifiants

Citer

Hilaire Bakala, Maud Hamelin, Jean Mary, Caroline Borot-Laloi, Bertrand Friguet. Catalase, a target of glycation damage in rat liver mitochondria with aging. Biochimica et Biophysica Acta - Molecular Basis of Disease, 2012, 1822 (10), pp.1527-1534. ⟨10.1016/j.bbadis.2012.05.016⟩. ⟨hal-01543994⟩
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