Attenuation of Muscle Atrophy by Triterpentene Celastrol

Heat stress has been found to attenuate atrophy of skeletal muscle in vivo and in vitro (Naito et al., 2000; Westerheide et al., 2004). This anti-atrophy effect is known to involve induction of heat shock proteins (HSPs) like HSP72, an important molecular chaperone for protein quality control. For instance, hindlimb-unloaded rats whose body temperature was raised to 41.6oC by mild heat showed a significant retention of muscle mass, concurrently with significant upregulation of HSP72 expression, compared to the vivarium control. Muscle atrophy occurs when the proteoytic rate exceeds the anabolic rate (Hoffman and Nader, 2004). Because HSPs play a critical role in folding and repair of proteins as well as cytoprotection against external stresses (e.g., hyperthermia and physical stress) (Naito et al., 2000), it is reasonable to consider that upregulation of HSPs aid not only to elevate protein anabolism but also to reduce protein degradation. Moreover, since these proteins are crucial for organization and protection of myofilaments (Srikakulam and Winkelmann, 2004), structural integrity of myofibrils can be stabilized by upregulation of HSPs even in the unloaded state.