Involvement of released sphingosine 1-phosphate/sphingosine 1-phosphate receptor axis in skeletal muscle atrophy
| Autor: | Elisabetta Meacci, Maria Chiara Iachini, Fabio Penna, Federica Pierucci, Francesca Matteini, Paola Costelli, Chiara Battistini, Ambra Vestri, Alessia Frati |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Atrogin-1 Cell autophagy S1P receptor (S1PR) S1P transporter Spns2 Skeletal muscle mass waste Sphingosine 1-phosphate Molecular Medicine Molecular Biology Muscle Fibers Skeletal Sphingosine kinase Protein degradation Dexamethasone Cell Line 03 medical and health sciences chemistry.chemical_compound Sphingosine Neoplasms medicine Animals Myocyte Sphingosine-1-phosphate Mice Inbred BALB C biology Myogenesis Skeletal muscle Ubiquitin ligase Cell biology Muscular Atrophy Phosphotransferases (Alcohol Group Acceptor) Receptors Lysosphingolipid 030104 developmental biology medicine.anatomical_structure chemistry biology.protein Female Lysophospholipids Signal Transduction |
| Popis: | Skeletal muscle (SkM) atrophy is caused by several and heterogeneous conditions, such as cancer, neuromuscular disorders and aging. In most types of SkM atrophy overall rates of protein synthesis are suppressed, protein degradation is consistently elevated and atrogenes, such as the ubiquitin ligase Atrogin-1/MAFbx, are up-regulated. The molecular regulators of SkM waste are multiple and only in part known. Sphingolipids represent a class of bioactive molecules capable of modulating the destiny of many cell types, including SkM cells. In particular, we and others have shown that sphingosine 1phosphate (S1P), formed by sphingosine kinase (SphK), is able to act as trophic and morphogenic factor in myoblasts. Here, we report the first evidence that the atrophic phenotype observed in both muscle obtained from mice bearing the C26 adenocarcinoma and C2C12 myotubes treated with dexamethasone was characterized by reduced levels of active phospho-SphK1. The importance of SphK1 activity is also confirmed by the specific pharmacological inhibition of SphK1 able to increase Atrogin-1/MAFbx expression and reduce myotube size and myonuclei number. Furthermore, we found that SkM atrophy was accomplished by significant increase of S1P transporter Spns2 and in changes in the pattern of S1P receptor (S1PRs) subtype expression paralleled by increased Atrogin-1/MAFbx expression, suggesting a role for the released S1P and of specific S1PR-mediated signaling pathways in the control of the ubiquitin ligase. Altogether, these findings provide the first evidence that SphK1/released S1P/S1PR axis acts as a molecular regulator of SkM atrophy, thereby representing a new possible target for therapy in many patho-physiological conditions. |
| Databáze: | OpenAIRE |
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