Abstract
It is well known that functional unloading leads to a number of complex changes in the lipid-protein structural components in the sarcolemmal compartment of postural muscles' fibers. Among these changes are an increase of the sarcolemmal ceramide content, loss in cholesterol density in the lipid rafts fraction, a decrease of membrane sphingomyelin as a result of acid sphingomyelinase (ASM) activation and enhanced hydrolysis of sphingomyelin. These changes may underlie damages and primary elimination of damaged parts of muscle fibers' plasma membrane. Secondary reparation of sarcolemma depends on reorganization of the subsarcolemmal cytoskeleton. It appears to be exocytosis of caveolin-enriched vesicles in response to the growth of ASM dependent hydrolysis in the plasma membrane of muscle fibers. In our study, immunofluorescence microscopy and Western blot analysis were used to investigate ceramide and caveolin-3 changes in the sarcolemmal compartment of muscle fibers and total m. soleus from rats subjected to 14-d hindlimb unloading or unloading with administration of ASM inhibitor amitriptyline. In addition, muscle preparations with added exogenous sphingomyelinase were subjected to ex vivo analysis of ceramide and caveolin-3 immunofluorescence. The 14-d unloading led to the growth of ceramide and caveolin-3 immunofluorescence on muscle sections. Ex vivo analysis also demonstrated a significant increase of ceramide and caveolin-3 content in muscle fibers exposed to exogenous sphingomyelinase. The increase of caveolin-3 sarcolemmal density was confirmed by Western blot assay which indicated the growth of its amount in isolated sarcolemmal fraction. These changes were not observed in total homogenates of the unloaded m. soleus. Thus, functional unloading of the postural muscle leads to the accumulation of ceramide in the plasma membrane of muscle fibers and an increase in the level of membrane caveolin-3.
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