Cardiac overexpression of antioxidant catalase attenuates aging-induced cardiomyocyte relaxation dysfunction.

Abstract Catalase, an enzyme which detoxifies H 2 O 2 , may interfere with cardiac aging. To test this hypothesis, contractile and intracellular Ca 2+ properties were evaluated in cardiomyocytes from young (3–4 months) and old (26–28 months) FVB and transgenic mice with cardiac overexpression of catalase. Contractile indices analyzed included peak shortening (PS), time-to-90% PS (TPS 90 ), time-to-90% relengthening (TR 90 ), half-width duration (HWD), maximal velocity of shortening/relengthening (±d L /d t ) and intracellular Ca 2+ levels or decay rate. Levels of advanced glycation endproduct (AGE), Na + /Ca 2+ exchanger (NCX), sarco(endo)plasmic reticulum Ca 2+ -ATPase (SERCA2a), phospholamban (PLB), myosin heavy chain (MHC), membrane Ca 2+ and K + channels were measured by western blot. Catalase transgene prolonged survival while did not alter myocyte function by itself. Aging depressed ±d L /d t , prolonged HWD, TR 90 and intracellular Ca 2+ decay without affecting other indices in FVB myocytes. Aged FVB myocytes exhibited a stepper decline in PS in response to elevated stimulus or a dampened rise in PS in response to elevated extracellular Ca 2+ levels. Interestingly, aging-induced defects were nullified or significantly attenuated by catalase. AGE level was elevated by 5-fold in aged FVB compared with young FVB mice, which was reduced by catalase. Expression of SERCA2a, NCX and Kv 1.2 K + channel was significantly reduced although levels of PLB, L-type Ca 2+ channel dihydropyridine receptor and β-MHC isozyme remained unchanged in aged FVB hearts. Catalase restored NCX and Kv 1.2 K + channel but not SERCA2a level in aged mice. In summary, our data suggested that catalase protects cardiomyocytes from aging-induced contractile defect possibly via improved intracellular Ca 2+ handling.