Effects of prior chronic contractile activity on subsequent denervation‐induced apoptosis in skeletal muscle

Abstract

We have previously shown that chronic muscle denervation results in an increase in mitochondrially-mediated apoptosis. This study was designed to evaluate whether contractile activity of the rat tibialis anterior (TA) muscle, using 7 days of chronic stimulation prior to 7 days of denervation, could attenuate the progression of apoptosis. Denervation led to 35–40% decreases in COX activity and subsarcolemmal (SS) mitochondrial content. Prior contractile activity attenuated these decrements, and maintained both COX activity and SS mitochondrial content at control levels. However, prior contractile activity did not prevent the denervation-induced decreases in mitochondrial state 3 respiration. Denervation resulted in a 50% increase in intermyofibrillar (IMF) mitochondrial reactive oxygen species production, and a 27% decrease in MnSOD expression. These adaptations were prevented by prior contractile activity. Denervation also induced a 2.2-fold increase in Bax expression. This increase was not reduced by prior contractile activity. Thus, pre-conditioning of skeletal muscle using chronic contractile activity prior to denervation maintained muscle COX activity and SS mitochondrial content, reduced IMF mitochondrial oxidative stress, but did not attenuate the denervation-induced increases in pro-apoptotic protein expression.