Acute high-intensity aerobic exercise increases gene expression of calcium-related proteins and activates endoplasmic reticulum stress responses in diabetic hearts

Abstract

Regular aerobic exercise training has a wide range of beneficial cardiac effects, but recent data also show that acute very strenuous aerobic exercise may impose a transient cardiac exhaustion. The aim of this study was to assess the response to acute high-intensity aerobic exercise on properties of mitochondrial respiration, cardiomyocyte contractile function, Ca2+ handling and transcriptional changes for key proteins facilitating Ca2+ handling and endoplasmic reticulum (ER) stress responses in type 2 diabetic mice. Diabetic mice were assigned to either sedentary control or an acute bout of exercise, consisting of a 10×4 minutes high-intensity interval treadmill run. Mitochondrial respiration, contractile and Ca2+ handling properties of cardiomyocytes were analysed 1 hour after completion of exercise. Gene expression levels of key Ca2+ handling and ER stress response proteins were measured in cardiac tissue samples harvested 1 hour and 24 hours after exercise. We found no significant changes in mitochondrial respiration, cardiomyocyte contractile function or Ca2+ handling 1 hour after the acute exercise. However, gene expression of Atp2a2, Slc8a1 and Ryr2, encoding proteins involved in cardiomyocyte Ca2+ handling, were all significantly upregulated 24 hours after the acute exercise bout. Acute exercise also altered gene expression of several key proteins in ER stress response and unfolded protein response, including Grp94, total Xbp1, Gadd34, and Atf6. The present results show that despite no significant alterations in functional properties of cardiomyocyte function, Ca2+ handling or mitochondrial respiration following one bout of high intensity aerobic exercise training, the expression of genes involved in Ca2+ handling and key components in ER stress and the unfolded protein response were changed. These transcriptional changes may constitute important steps in initiating adaptive remodelling to exercise training in type 2 diabetes.