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• W2169220342 abstract "Myocyte contractile dysfunction occurs in pathological remodeling in association with abnormalities in calcium regulation. Mice with cardiac myocyte-specific overexpression of Galphaq develop progressive left ventricular failure associated with myocyte contractile dysfunction and calcium dysregulation.We tested the hypothesis that myocyte contractile dysfunction in the Galphaq mouse heart is mediated by reactive oxygen species, and in particular, oxidative posttranslational modifications, which impair the function of sarcoplasmic reticulum Ca2+-ATPase (SERCA).Freshly isolated ventricular myocytes from Galphaq mice had marked abnormalities of myocyte contractile function and calcium transients. In Galphaq myocardium, SERCA protein was not altered in quantity but displayed evidence of oxidative cysteine modifications reflected by decreased biotinylated iodoacetamide labeling and evidence of specific irreversible oxidative modifications consisting of sulfonylation at cysteine 674 and nitration at tyrosines 294/295. Maximal calcium-stimulated SERCA activity was decreased 47% in Galphaq myocardium. Cross-breeding Galphaq mice with transgenic mice that have cardiac myocyte-specific overexpression of catalase (a) decreased SERCA oxidative cysteine modifications, (b) decreased SERCA cysteine 674 sulfonylation and tyrosine 294/295 nitration, (c) restored SERCA activity, and (d) improved myocyte calcium transients and contractile function.In Galphaq-induced cardiomyopathy, myocyte contractile dysfunction is mediated, at least in part, by 1 or more oxidative posttranslational modifications of SERCA. Protein oxidative posttranslational modifications contribute to the pathophysiology of myocardial dysfunction and thus may provide a target for therapeutic intervention." @default.
• W2169220342 created "2016-06-24" @default.
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• W2169220342 date "2010-07-23" @default.
• W2169220342 modified "2023-10-12" @default.
• W2169220342 title "Short Communication: Oxidative Posttranslational Modifications Mediate Decreased SERCA Activity and Myocyte Dysfunction in Gαq-Overexpressing Mice" @default.
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• W2169220342 doi "https://doi.org/10.1161/circresaha.110.217570" @default.
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