Effects of IFN-γ on FoxO1 acetylation and activity in mouse myoblast cells and its mechanism
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    Abstract:

    Objective:To investigate the activity and acetylation of FoxO1 after inflammatory cytokine IFN-γ treatment in mouse myoblast cells(C2C12) and its regulatory mechanisms on T2DM. Methods:Acetylation of FoxO1 after IFN-γ and silent information regulator 1 (SIRT1) activator resveratrol treatment were evaluated by co-immunoprecipitation (co-IP) followed by Western blot. Luciferase reporter assays were performed to assess the effect of IFN-γ and C Ⅱ TA on the promoter activities of FoxO1. To evaluate whether CⅡTA was necessary for the repression of SIRT1 activity by IFN-γ,cells were transfected with C Ⅱ TA small interfering RNA(siRNA). Results:IFN-γ augmented the acetylation level of FoxO1 while down-regulated by resveratrol. IFN-γ suppressed the transcriptional activity of wild-type FoxO1,mutation of lysine residues in FoxO1 abrogated such effects. C Ⅱ TA directly inhibited FoxO1 dependent transcription and while transfected with FoxO1 simultaneously,the inhibition was up to 60%. C Ⅱ TA depletion restored FoxO1 transcriptional activity in the presence of IFN-γ. Conclusion:IFN-γ induced the expression of C Ⅱ TA,which in turn inhibited SIRT1 enzyme activity,increased the acetylation level of FoxO1,thus reduced its transcriptional activity. Therefore,our study provides a potential target for clinical intervention in T2DM.

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方明明,吴晓燕,李 平,袁艺标.炎症因子IFN-γ调控小鼠成肌细胞FoxO1乙酰化及活性的机制研究[J].南京医科大学学报(自然科学版英文版),2016,(11):1316-1320.

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  • Received:May 07,2016
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  • Online: November 28,2016
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