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

The purpose of this review is to summarize data supporting the idea that ceramide may affect some intracellular processes associated with the of skeletal muscle myosin phenotype caused by disuse. Postural muscles, such as soleus, are characterized by prevailing of slow-twitch fibers, which express predominantly a type I myosin heavy chain (MyHC 1). Soleus muscle unloading leads to the shift of slow to fast MyHC expression. It is well documented that this phenomenon may be associated with the suppression of the calcium-dependent calcineurin- nuclear factor of activated T-cells (NFAT1) pathway. The role of other mechanisms, including signaling by AMP-activated kinase (AMPK), glycogen synthase kinase-3 (GSK-3β), myoblast determination protein 1 (MyoD), histone deacetylases (HDAC), is also widely discussed in the literature. It has been shown that unloading leads to the accumulation of ceramides in muscles both in early (6–12 hours) and longer (4–14 days) periods of inactivity. In skeletal muscles, ceramide can affect some molecular processes that are known to be involved in the regulation of MyHC expression. The known intracellular targets activated by ceramide directly or indirectly are stress-activated protein kinases (SAPK), atypical protein kinase C ζ (PKC ζ), protein phosphatase 2A (PP2A), GSK-3 and others. This review is focused on the analysis of data indicating the possible participation of ceramide in the remodeling of skeletal muscle myosin phenotype during disuse.