Muscle Plasticity under Functional Unloading: Effects of an Acid Sphingomyelinase Inhibitor Clomipramine
Sphingolipids function as both structural components of cells and intracellular messengers. The role of sphingolipids, including ceramide, in the regulation of muscle plasticity has not been studied. The present work aimed to study the effect of an inhibitor of the catalytic pathway of ceramide form...
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Veröffentlicht in: | Journal of evolutionary biochemistry and physiology 2021-07, Vol.57 (4), p.925-935 |
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Sprache: | eng |
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Zusammenfassung: | Sphingolipids function as both structural components of cells and intracellular messengers. The role of sphingolipids, including ceramide, in the regulation of muscle plasticity has not been studied. The present work aimed to study the effect of an inhibitor of the catalytic pathway of ceramide formation on the expression of myosin heavy chains (MyHC), atrophy, p-mTOR (Ser2484) and p-p70S6 kinase (Thr389) protein levels in the postural muscle (
m. soleus
) under conditions of functional unloading. Experiments were carried out on male Wistar rats (180−230 g). To reproduce muscle unloading, the hindlimb suspension (HS) model was used. We determined the signs of muscle atrophy (changes in muscle mass and the Feret’s diameter of muscle fibers), levels of ceramide (thin-layer chromatography) and mTOR signaling system proteins (Western blotting), as well as the expression of fast and slow MyHC isoforms (qPCR, immunofluorescence study). In suspended
m. soleus
, we found a decrease in p-mTOR (Ser2484) and p-p70S6k (Thr389) levels, which was prevented by the administration of an acid sphingomyelinase (aSMase) inhibitor clomipramine. Clomipramine was also found to abolish a muscle phenotype shift toward the expression of fast MyHC isoforms (MyHC IIB and MyHC IId/x) and to reduce the degree of muscle atrophy. These results indicate the role of the sphingolipid mechanisms in the disruption of mTOR signaling, dysregulation of the expression of fast MyHC isoforms, and development of muscle atrophy caused by functional unloading. |
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ISSN: | 0022-0930 1608-3202 |
DOI: | 10.1134/S0022093021040165 |