Increased expression of heat shock proteins in skeletal muscle induces autophagy

Abstract

PURPOSETo determine if heat shock proteins (hsp) are involved in autophagy in mouse skeletal muscle.METHODSTo determine whether an hsp activator stimulates autophagy in skeletal muscle, CB6F1 wild‐type mice were i.p. injected with 17‐DMAG (a hsp activator, 10 mg/kg) daily for 6 days with and without colchicine (autophagy inhibitor, 0.4 mg/kg/day) administration in the last 2 days to measure in vivo autophagic flux in skeletal muscle. In order to induce autophagy, mice were also treated with rapamycin (10 mg/kg i.p.) for 2 days with and without 2 days of colchicine administration. Tibialis anterior muscles were excised and p62/SQSTM1 and LC3 II (autophagic marker proteins) were analyzed by Western blot.RESULTSWestern blots show that p62 protein levels were significantly decreased (~50%; P<0.05) in 17‐DMAG and rapamycin treated mouse skeletal muscles. The LC3 II protein levels were increased even further when degradation was inhibited by colchicine in 17‐DMAG treated mice by ~2‐fold (P<0.01), similar results were obtained with rapamycin.CONCLUSIONOur study suggests that the heat shock proteins enhance autophagy in mouse skeletal muscle under basal and induced conditions, the precise mechanism by which the hsps regulate autophagy still needs to be clarified.This research was supported by an award from the USAMRMC.