Exercise-induced increases in the expression and activity of cardiac sarcoplasmic reticulum calcium ATPase 2 is attenuated in [AMPK[alpha].sub.2] kinase-dead mice

Exercise enhances cardiac sarcoplasmic reticulum [Ca.sup.2+]-ATPase 2a (SERCA2a) function through unknown mechanisms. The present study tested the hypothesis that the positive effects of exercise on SERCA2a expression and function in the left ventricle is dependent on adenosine-monophosphate-activat...

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Bibliographic Details
Published in:Canadian journal of physiology and pharmacology 2019-08, Vol.97 (8), p.786
Main Authors: Morissette, Marc P, Susser, Shanel E, Stammers, Andrew N, Moffatt, Teri L, Wigle, Jeffrey T, Wigle, Theodore J, Netticadan, Thomas, Premecz, Sheena, Jassal, Davinder S, O'Hara, Kimberley A, Duhamel, Todd A
Format: Article
Language:English
Subjects:
Adenosine triphosphatase
Genetic engineering
Mice
Physical fitness
Protein kinases
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Summary:Exercise enhances cardiac sarcoplasmic reticulum [Ca.sup.2+]-ATPase 2a (SERCA2a) function through unknown mechanisms. The present study tested the hypothesis that the positive effects of exercise on SERCA2a expression and function in the left ventricle is dependent on adenosine-monophosphate-activated protein kinase (AMPK) [[alpha].sub.2] function. [AMPK[alpha].sub.2] kinase-dead (KD) transgenic mice, which overexpress inactivated [AMPK[alpha].sub.2] subunit, and wild-type C57Bl/6 (WT) mice were randomized into sedentary groups or groups with access to running wheels. After 5 months, exercised KD mice exhibited shortened deceleration time compared with sedentary KD mice. In left ventricular tissue, the ratio of phosphorylated [AMPK[alpha].sup.Thr72]:total AMPK[alpha] was 65% lower (P < 0.05) in KD mice compared with WT mice. The left ventricle of KD mice had 37% lower levels of SERCA2a compared with WT mice. Although exercise increased SERCA2a protein levels in WT mice by 53%, this response of exercise was abolished in exercised KD mice. Exercise training reduced total phospholamban protein content by 23% in both the WT and KD mice but remained 20% higher overall in KD mice. Collectively, these data suggest that AMPK[alpha] influences SERCA2a and phospholamban protein content in the sedentary and exercised heart, and that exercise-induced changes in SERCA2a protein are dependent on AMPK[alpha] function.
ISSN:0008-4212
1205-7541
DOI:10.1139/cjpp-2018-0737