Lysophosphatidic Acid Signaling Axis Mediates Ceramide 1-Phosphate-Induced Proliferation of C2C12 Myoblasts
| Autor: | Chiara Donati, Alberto Ouro, Paola Bruni, Caterina Bernacchioni, Francesca Cencetti, Marina Bruno, Antonio Gómez-Muñoz |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Myoblast proliferation lysophosphatidic acid (LPA) ceramide 1-phosphate (C1P) lysophosphatidic acid receptor (LPAR) skeletal muscle myoblast proliferation lcsh:Chemistry Myoblasts Mice chemistry.chemical_compound 0302 clinical medicine Lysophosphatidic acid Myocyte Receptors Lysophosphatidic Acid Extracellular Signal-Regulated MAP Kinases lcsh:QH301-705.5 Spectroscopy General Medicine Computer Science Applications Cell biology medicine.anatomical_structure 030220 oncology & carcinogenesis C2C12 Signal Transduction Ceramide Ceramides Article Catalysis Cell Line Inorganic Chemistry 03 medical and health sciences Ceramide kinase medicine Animals Physical and Theoretical Chemistry Molecular Biology Protein kinase B Cell Proliferation Organic Chemistry Skeletal muscle Enzyme Activation Phospholipases A2 030104 developmental biology lcsh:Biology (General) lcsh:QD1-999 chemistry Cyclooxygenase 2 GTP-Binding Protein alpha Subunits Gq-G11 Lysophospholipids Mitogens Proto-Oncogene Proteins c-akt ceramide 1-phosphate lysophosphatidic acid lysophosphatidic acid receptor myoblast proliferation skeletal muscle |
| Zdroj: | International Journal of Molecular Sciences; Volume 19; Issue 1; Pages: 139 International Journal of Molecular Sciences International Journal of Molecular Sciences, Vol 19, Iss 1, p 139 (2018) |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms19010139 |
| Popis: | Sphingolipids are not only crucial for membrane architecture but act as critical regulators of cell functions. The bioactive sphingolipid ceramide 1-phosphate (C1P), generated by the action of ceramide kinase, has been reported to stimulate cell proliferation, cell migration and to regulate inflammatory responses via activation of different signaling pathways. We have previously shown that skeletal muscle is a tissue target for C1P since the phosphosphingolipid plays a positive role in myoblast proliferation implying a role in muscle regeneration. Skeletal muscle displays strong capacity of regeneration thanks to the presence of quiescent adult stem cells called satellite cells that upon trauma enter into the cell cycle and start proliferating. However, at present, the exact molecular mechanism by which C1P triggers its mitogenic effect in myoblasts is lacking. Here, we report for the first time that C1P stimulates C2C12 myoblast proliferation via lysophosphatidic acid (LPA) signaling axis. Indeed, C1P subsequently to phospholipase A2 activation leads to LPA1 and LPA3 engagement, which in turn drive Akt (protein kinase B) and ERK1/2 (extracellular signal-regulated kinases 1/2) activation, thus stimulating DNA synthesis. The present findings shed new light on the key role of bioactive sphingolipids in skeletal muscle and provide further support to the notion that these pleiotropic molecules might be useful therapeutic targets for skeletal muscle regeneration. |
| Databáze: | OpenAIRE |
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