Мышечная пластичность в условиях функциональной разгрузки: эффекты ингибитора кислой сфингомиелиназы кломипрамина

Abstract

Sphingolipids are the structural components of cells and intracellular messengers. The role of sphingolipids, including ceramide, in the regulation of muscle plasticity has not been studied. The purpose of the present work is to study the effect of an inhibitor of the catalytic pathway of ceramide formation on the expression of myosin heavy chains (MyHC), atrophy and the levels of mTOR / p-mTOR (Ser2484) / p70S6k proteins in the postural muscle (m. soleus) under conditions of functional unloading. The work was performed on male Wistar rats (180-230 g). To reproduce the unloading, the antiorthostatic suspension model (HS) was used. Signs of atrophy (changes in muscle mass and Feret’s diameter of muscle fibers), the amount of ceramide (TLC), mTOR signaling system proteins (Western blotting) and the expression of fast and slow isoforms of myosin heavy chains (PCR, immunofluorescence study) were determined. In suspended m. soleus, we found a decrease in the levels of p-mTOR (Ser2484) and p70S6k (Thr389), which was prevented by administration of the acid sphingomyelinase inhibitor (aSMase) clomipramine. The shift of the muscle phenotype towards the expression of fast myosin isoforms (MyHC IIB and MyHC IIx), a characteristic feature of HS, was also eliminated by clomipramine, along with the diminished muscle atrophy. The results obtained indicate the role of sphingolipid mechanisms in the disturbance of mTOR signaling, dysregulation of the expression of fast myosin isoforms and the development of muscle atrophy caused by functional unloading.