title: Cardiac overexpression of antioxidant catalase attenuates aging-induced cardiomyocyte relaxation dysfunction.
abstract: Catalase, an enzyme which detoxifies H2O2, may interfere with cardiac aging. To test this hypothesis, contractile and intracellular Ca2+ 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 (TPS90), time-to-90% relengthening (TR90), half-width duration (HWD), maximal velocity of shortening/relengthening (+/-dL/dt) and intracellular Ca2+ levels or decay rate. Levels of advanced glycation endproduct (AGE), Na+/Ca2+ exchanger (NCX), sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA2a), phospholamban (PLB), myosin heavy chain (MHC), membrane Ca2+ and K+ channels were measured by western blot. Catalase transgene prolonged survival while did not alter myocyte function by itself. Aging depressed+/-dL/dt, prolonged HWD, TR90 and intracellular Ca2+ 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 Ca2+ 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 Kv1.2 K+ channel was significantly reduced although levels of PLB, L-type Ca2+ channel dihydropyridine receptor and beta-MHC isozyme remained unchanged in aged FVB hearts. Catalase restored NCX and Kv1.2 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 Ca2+ handling.
authors.affiliation: Division of Pharmaceutical Sciences & Center for Cardiovascular Research and Alternative Medicine, University of Wyoming, Laramie, WY 82071-2000, United States. jren@uwyo.edu
authors.forename: Jun
authors.initials: J
authors.lastname: Ren
authors.forename: Qun
authors.initials: Q
authors.lastname: Li
authors.forename: Shan
authors.initials: S
authors.lastname: Wu
authors.forename: Shi-Yan
authors.initials: SY
authors.lastname: Li
authors.forename: Sara A
authors.initials: SA
authors.lastname: Babcock
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D015153:Blotting, Western; D020746:Calcium Channels, L-Type / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology; D002135:Calcium-Binding Proteins / Q000378:metabolism; D009202:Cardiomyopathies / Q000201:enzymology* / Q000503:physiopathology*; D002374:Catalase / Q000096:biosynthesis*; D004591:Electrophoresis, Polyacrylamide Gel; D017127:Glycation End Products, Advanced / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000201:enzymology*; D032383:Myocytes, Cardiac / Q000502:physiology*; D018995:Myosin Heavy Chains / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D020675:Peroxisomes / Q000201:enzymology; D015221:Potassium Channels / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000502:physiology; D012519:Sarcoplasmic Reticulum / Q000201:enzymology; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000378:metabolism; D013534:Survival; D000099211:Phospholamban
chemical_list: D000975:Antioxidants; D020746:Calcium Channels, L-Type; D002135:Calcium-Binding Proteins; D002374:Catalase; D017127:Glycation End Products, Advanced; D007527:Isoenzymes; D018995:Myosin Heavy Chains; D015221:Potassium Channels; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D019831:Sodium-Calcium Exchanger; D000099211:Phospholamban