Age-dependent increase in hydrogen peroxide production by cardiac monoamine oxidase A in rats

Unité 388, Institut National de la Santé et de la Recherche Médicale, Institut Louis Bugnard, Centre Hospitalier Universitaire Rangueil, 31403 Toulouse cedex 04, France Oxidative stress is one of the factors involved in age-related impairment of cardiac function. In the present study, we investigated the role of the catecholamine-degrading enzyme monoamine oxidase (MAO) in H 2 O 2 production in the hearts of young, adult, and old rats. MAO-dependent H 2 O 2 production, measured by a chemiluminescence-based assay, increased with age, reaching the maximum in 24-mo-old rats (7.5-fold increase vs. 1-mo-old rats). The following observations indicate that the age-dependent increase in H 2 O 2 generation was fully related to the MAO-A isoform: 1 ) at all the ages tested, chemiluminescence production was inhibited by the MAO-A inhibitor clorgyline but not by the MAO-B inhibitor RO-19 6327; 2 ) enzyme assay, Western blot, and semiquantitative RT-PCR analysis showed an age-dependent increase in cardiac MAO-A activity, immunodetection, and mRNA expression, respectively; and 3 ) the MAO-B isoform was undetectable by enzyme assay and Western blot analysis. These results suggest that MAO-A could be a major source of H 2 O 2 in the aging heart. monoamine oxidases; oxidative stress