Control of Skeletal Muscle Atrophy Associated to Cancer or Corticosteroids by Ceramide Kinase

Apart from cytokines and chemokines, sphingolipid mediators, particularly sphingosine-1-phosphate (S1P) ceramide 1-phosphate (C1P), contribute to cancer inflammation. Cancer, as well other inflammatory conditions, are associated with skeletal muscle (SkM) atrophy, which is characterized by the unbalance between protein synthesis degradation. Although signaling pathways involved in SkM mass wasting multiple, regulatory role of simple sphingolipids limited. Here, we report impairment kinase (CerK), enzyme responsible for phosphorylation C1P, accomplishment atrophic phenotype various experimental models atrophy: vivo animal model bearing C26 adenocarcinoma or Lewis lung carcinoma tumors, human murine cells treated conditioned medium obtained glucocorticoid dexamethasone. Notably, demonstrate all three approaches a drastic decrease CerK expression. Gene silencing promotes up-regulation atrogin-1/MAFbx expression, was also observed after cell treatment C8-ceramide, biologically active analogue. Conversely, C1P significantly reduced corticosteroid’s effects. Altogether, these findings provide evidence that CerK, acting molecular modulator, may be new possible target regulation corticosteroids.