Role of Ceramide in Remodeling of Skeletal Muscle Myosin Phenotype during Disuse: Possible Mechanisms

The purpose of this review is to summarize data supportingthe idea that ceramide may affect some intracellular processes associatedwith the of skeletal muscle myosin phenotype caused by disuse. Posturalmuscles, such as soleus, are characterized by prevailing of slow-twitchfibers, which express predominantly a type I myosin heavy chain(MyHC 1). Soleus muscle unloading leads to the shift of slow tofast MyHC expression. It is well documented that this phenomenonmay be associated with the suppression of the calcium-dependentcalcineurin- nuclear factor of activated T-cells (NFAT1) pathway.The role of other mechanisms, including signaling by AMP-activatedkinase (AMPK), glycogen synthase kinase-3 (GSK-3β), myoblast determinationprotein 1 (MyoD), histone deacetylases (HDAC), is also widely discussedin the literature. It has been shown that unloading leads to the accumulationof ceramides in muscles both in early (6–12 hours) and longer (4–14days) periods of inactivity. In skeletal muscles, ceramide can affectsome molecular processes that are known to be involved in the regulationof MyHC expression. The known intracellular targets activated byceramide directly or indirectly are stress-activated protein kinases(SAPK), atypical protein kinase C ζ (PKC ζ), protein phosphatase2A (PP2A), GSK-3 and others. This review is focused on the analysisof data indicating the possible participation of ceramide in theremodeling of skeletal muscle myosin phenotype during disuse.