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Cardiac overexpression of alcohol dehydrogenase (ADH) alleviates aging-associated cardiomyocyte contractile dysfunction: role of intracellular Ca2+ cycling proteins.
Aging Cell. 2006 Jun; 5(3):259-65.AC

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 Ca(2+)-ATPase (SERCA2a) and Na(+)-Ca(2+) 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 Ca(2+) cycling proteins including SERCA2a and NCX may play a role in both pathogenesis of cardiac aging and the beneficial effect of ADH enzyme.

Authors+Show Affiliations

Division of Pharmaceutical Sciences & Center for Cardiovascular Research and Alternative Medicine, University of Wyoming, Laramie, WY 82071, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

16842498

Citation

Guo, Kelly K., and Jun Ren. "Cardiac Overexpression of Alcohol Dehydrogenase (ADH) Alleviates Aging-associated Cardiomyocyte Contractile Dysfunction: Role of Intracellular Ca2+ Cycling Proteins." Aging Cell, vol. 5, no. 3, 2006, pp. 259-65.
Guo KK, Ren J. Cardiac overexpression of alcohol dehydrogenase (ADH) alleviates aging-associated cardiomyocyte contractile dysfunction: role of intracellular Ca2+ cycling proteins. Aging Cell. 2006;5(3):259-65.
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), 259-65.
Guo KK, Ren J. Cardiac Overexpression of Alcohol Dehydrogenase (ADH) Alleviates Aging-associated Cardiomyocyte Contractile Dysfunction: Role of Intracellular Ca2+ Cycling Proteins. Aging Cell. 2006;5(3):259-65. PubMed PMID: 16842498.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cardiac overexpression of alcohol dehydrogenase (ADH) alleviates aging-associated cardiomyocyte contractile dysfunction: role of intracellular Ca2+ cycling proteins. AU - Guo,Kelly K, AU - Ren,Jun, PY - 2006/7/18/pubmed PY - 2006/9/6/medline PY - 2006/7/18/entrez SP - 259 EP - 65 JF - Aging cell JO - Aging Cell VL - 5 IS - 3 N2 - 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 Ca(2+)-ATPase (SERCA2a) and Na(+)-Ca(2+) 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 Ca(2+) cycling proteins including SERCA2a and NCX may play a role in both pathogenesis of cardiac aging and the beneficial effect of ADH enzyme. SN - 1474-9718 UR - https://www.unboundmedicine.com/medline/citation/16842498/Cardiac_overexpression_of_alcohol_dehydrogenase__ADH__alleviates_aging_associated_cardiomyocyte_contractile_dysfunction:_role_of_intracellular_Ca2+_cycling_proteins_ L2 - https://doi.org/10.1111/j.1474-9726.2006.00215.x DB - PRIME DP - Unbound Medicine ER -