AMPK/FOXO1 signaling pathway is indispensable in visfatin-regulated myosin heavy chain expression in C2C12 myotubes
AMPK/FOXO1 signaling pathway is indispensable in visfatin-regulated myosin heavy chain expression in C2C12 myotubes
复制标题
AMPK/FOXO1 信号通路在 C2C12 肌管中内脂素调节肌球蛋白重链表达中不可或缺
DOI：
10.1016/j.lfs.2019.03.060
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发表时间：
2019
期刊：
影响因子：
6.1
通讯作者：
Li Qing Yun
中科院分区：
文献类型：
--
作者：
Zhou Li Na;Lin Ying Ni;Gu Chen Juan;Zhou Jian Ping;Sun Xian Wen;Cai Xiao Ting;Du Juan;Li Qing Yun
目的研究visfatin对骨骼肌重塑的影响。本研究旨在探讨visfatin对骨骼肌纤维类型和收缩特性的主要指标肌球蛋白重链（myosin heavy chain， MHC）及其异构体表达的影响。材料与方法检测visfatin处理的C2C12肌管中MHC、MHC I、MHC IIa、MHC IIb、腺苷5′-单磷酸腺苷（AMP）活化蛋白激酶（AMPK）、p-AMPK和叉头盒蛋白O1 （FOXO1）的水平。用visfatin联合AMPK抑制剂或AMPK激活剂处理C2C12肌管，研究AMPK在visfatin介导的MHC表达中的作用。FOXO1在C2C12肌管中过表达或敲低，探讨FOXO1在visfatin介导的MHC表达中的作用。结果与对照组比较，5 μg/ml visfatin使总MHC及其亚型MHC I、MHC IIa和MHC IIb水平分别提高1.93倍、1.84倍、1.80倍和1.92倍（均p= 0.001）。Visfatin抑制AMPK磷酸化，降低C2C12肌管中FOXO1的表达。visfatin对MHC I和MHC IIa表达的影响被AMPK激活剂AICAR抵消。FOXO1过表达降低了visfatin诱导的MHC I、MHC IIa和MHC IIb的上调。AMPK激活剂AICAR对MHC及其亚型表达的影响通过敲除FOXO1最小化。结论visfatin通过抑制AMPK/FOXO1信号通路促进C2C12肌管中MHC及其亚型的表达。
ObjectiveFew studies have addressed the effects of visfatin on skeletal muscle remodeling. The aim of the study was to investigate the effects of visfatin on the expressions of myosin heavy chain (MHC) and its isoforms, the major indicator of fiber types and contractile properties of skeletal muscle.Materials and methodsLevels of MHC, MHC I, MHC IIa, MHC IIb, adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK), p-AMPK and forkhead box protein O1 (FOXO1) were tested in visfatin-treated C2C12 myotubes. C2C12 myotubes were treated with visfatin combined with AMPK inhibitor or AMPK activator to investigate the role of AMPK in visfatin-mediated MHC expression. FOXO1 was overexpressed or knocked down in C2C12 myotubes to explore the role of FOXO1 in visfatin-mediated MHC expression.ResultsCompared with the vehicle group, treatment with 5 μg/ml visfatin increased the levels of total MHC and its isoforms, MHC I, MHC IIa and MHC IIb, by 1.93, 1.84, 1.80, and 1.92 folds, respectively (allp= 0,001). Visfatin suppressed AMPK phosphorylation and decreased FOXO1 expression in C2C12 myotubes. The effects of visfatin on MHC I and MHC IIa expression were canceled by AMPK activator AICAR. FOXO1 overexpression minimized the visfatin-induced upregulation of MHC I, MHC IIa and MHC IIb. The effect of AMPK activator AICAR on MHC and its isoforms expression was minimized by knockdown of FOXO1.ConclusionsThe findings revealed that visfatin promoted expressions of MHC and its isoforms in C2C12 myotubes via suppressing AMPK/FOXO1 signaling pathway.