کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1919305 | 1535616 | 2013 | 12 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Metformin limits ceramide-induced senescence in C2C12 myoblasts Metformin limits ceramide-induced senescence in C2C12 myoblasts](/preview/png/1919305.png)
• Jadhav et al. entitled “Metformin limits ceramide-induced senescence in C2C12 myoblasts”.
• Insulin-resistant myoblasts display reduced cell proliferation and cell cycle, and associated cell senescence.
• Ceramide treatment of myoblasts works through a p53-dependent mechanism.
• Prior treatment with metformin mitigates ceramides effects on cell cycle and cell senescence in muscle cultures.
High lipid and ceramide concentrations are hallmarks of obese and/or insulin resistant skeletal muscle, yet little is known about its role on cell cycle and senescence. The purpose of this study was to examine the role of ceramide on muscle senescence, and whether metformin limited this response.MethodsLow passage, proliferating C2C12 myoblasts were treated with a control, 50 μM C2-ceramide (8 h), and/or 2 mM metformin, then examined for insulin sensitivity, cell senescence, cell proliferation, cell cycle, protein expression of cell cycle regulators.ResultsCeramide treatment caused a dephosphorylation (p < 0.05) of Akt and 4E-BP1, regardless of the presence of insulin. The ceramide treated myoblasts displayed higher β-galactosidase staining (p < 0.05), reduced BrDu incorporation and total number of cells (p < 0.05), and an increased proportion of cells in G2-phase (p < 0.05) versus control cultures. Ceramide treatment also upregulated (p < 0.05) p53 and p21 protein expression, that was reversed by either pifithrin-α or shRNA for p53. Metformin limited (p < 0.05) ceramide's effects on insulin signaling, senescence, and cell cycle regulation.ConclusionsHigh ceramide concentrations reduced myoblast proliferation that was associated with aberrant cell cycle regulation and a senescent phenotype, which could provide an understanding of skeletal muscle cell adaptation during conditions of high intramuscular lipid deposition and/or obesity.
Journal: Mechanisms of Ageing and Development - Volume 134, Issues 11–12, November–December 2013, Pages 548–559