Adverse Effects of AMP-Activated Protein Kinase alpha 2-Subunit Deletion and High-Fat Diet on Heart Function and Ischemic Tolerance in Aged Female Mice

作者：Slamova K; Papousek F; Janovska P; Kopecky J; Kolar F

来源：Physiological Research, 2016, 65(1): 33-42.

DOI：10.33549/physiolres.932979

<jats:p>AMP-activated protein kinase (AMPK) plays a role in metabolic regulation under stress conditions, and inadequate AMPK signaling may be also involved in aging process. The aim was to find out whether AMPK α2-subunit deletion affects heart function and ischemic tolerance of adult and aged mice. AMPK α2-/- (KO) and wild type (WT) female mice were compared at the age of 6 and 18 months. KO mice exhibited subtle myocardial AMPK α2-subunit protein level, but no difference in AMPK α1-subunit was detected between the strains. Both α1- and α2-subunits of AMPK and their phosphorylation decreased with advanced age. Left ventricular fractional shortening was lower in KO than in WT mice of both age groups and this difference was maintained after high-fat feeding. Infarct size induced by global ischemia/reperfusion of isolated hearts was similar in both strains at 6 months of age. Aged WT but not KO mice exhibited improved ischemic tolerance compared with the younger group. High-fat feeding for 6 months during aging abolished the infarct size-reduction in WT without affecting KO animals; nevertheless, the extent of injury remained larger in KO mice. The results demonstrate that adverse effects of AMPK α2-subunit deletion and high-fat feeding on heart function and myocardial ischemic tolerance in aged female mice are not additive.</jats:p>

• 出版日期2016