Cardiac overexpression of alcohol dehydrogenase (ADH) alleviates aging-associated cardiomyocyte contractile dysfunction: Role of intracellular Ca2+ cycling proteins

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Abstract

Aging is a complex biological process with contributions from a wide variety of genes including insulin-like growth factor I and alcohol dehydrogenase (ADH), which decline with advanced age. The goal of this study was to examine if ADH enzyme plays any role in cardiac aging. Ventricular myocytes were isolated from young (2-3 months old) or aged (26-28 months old) male FVB wild-type and cardiac-specific ADH (class I, isozyme type 1) transgenic mice. Mechanical properties were measured using an IonOptix system. Aged FVB myocytes displayed significantly reduced ADH activity compared with young ones, which was restored by the ADH transgene. Compared with young cardiomyocytes, aged FVB myocytes exhibited prolonged relengthening duration and a steaper decline in peak shortening amplitude in response to elevated electrical stimuli. Although ADH transgene itself did not alter mechanical properties in young mice, it rescued aging-associated diastolic dysfunction without affecting dampened contractile response to high stimulus frequency. Immunoblot analysis revealed reduced sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA2a) and Na+-Ca2+ exchanger (NCX) levels in conjunction with enhanced phospholamban expression in aged FVB hearts. ADH transgene prevented aging-induced reduction in SERCA2a and NCX without affecting up-regulated phospholamban. Our data suggest that aging is associated with a reduced ADH enzymatic activity and diastolic dysfunction, which may be corrected with cardiac overexpression of the ADH enzyme. Alteration in cardiac Ca2+ cycling proteins including SERCA2a and NCX may play a role in both pathogenesis of cardiac aging and the beneficial effect of ADH enzyme. © 2006 The Authors Journal compilation © Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland 2006.

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APA

Guo, K. K., & Ren, J. (2006). Cardiac overexpression of alcohol dehydrogenase (ADH) alleviates aging-associated cardiomyocyte contractile dysfunction: Role of intracellular Ca2+ cycling proteins. Aging Cell, 5(3), 259–265. https://doi.org/10.1111/j.1474-9726.2006.00215.x

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