Age-dependent increase in hydrogen peroxide production by cardiac monoamine oxidase A in rats.
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.
Maurel
Agnès
A
Unité 388, Institut National de la Santé et de la Recherche Médicale, Institut Louis Bugnard, Centre Hospitalier Universitaire Rangueil, 31403 Toulouse cedex 04, France.
Hernandez
Carole
C
Kunduzova
Oksana
O
Bompart
Guy
G
Cambon
Claudie
C
Parini
Angelo
A
Francés
Bernard
B
D000375:Aging; D000818:Animals; D015153:Blotting, Western; D002462:Cell Membrane / Q000201:enzymology; D003010:Clorgyline / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007700:Kinetics; D008163:Luminescent Measurements; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009206:Myocardium / Q000201:enzymology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
D008996:Monoamine Oxidase Inhibitors; D012333:RNA, Messenger; D006861:Hydrogen Peroxide; D008995:Monoamine Oxidase; D003010:Clorgyline