期刊
JOURNAL OF CELLULAR BIOCHEMISTRY
卷 113, 期 4, 页码 1170-1181出版社
WILEY
DOI: 10.1002/jcb.23444
关键词
1a; 25(OH)2D3; C2C12 MUSCLE CELLS; Akt AND MYOGENESIS
资金
- Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET)
- Universidad Nacional del Sur, Argentina
We previously reported that 1a,25-dihydroxy-vitamin D3 [1a,25(OH)2D3] induces non-transcriptional rapid responses through activation of Src and MAPKs in the skeletal muscle cell line C2C12. In the present study we investigated the modulation of Akt by the secosteroid hormone in C2C12 cells at proliferative stage (myoblasts) and at early differentiation stage. In proliferating cells, 1a,25(OH)2D3 activates Akt by phosphorylation in Ser473 in a time-dependent manner (560?min). When these cells were pretreated with methyl-beta-cyclodextrin to disrupt caveolae microdomains, hormone-induced activation of Akt was suppressed. Similar results were obtained by siRNA silencing of caveolin-1 expression, further indicating that hormone effects on cell membrane caveolae are required for downstream signaling. PI3K and p38 MAPK, but not ERK1/2, participate in 1a,25(OH)2D3 activation of Akt in myoblasts. The involvement of p38 MAPK in Akt phosphorylation by the hormone probably occurs through MAPK-activated protein kinase 2 (MK2), which is activated by the steroid. In addition, the participation of Src in Akt phosphorylation by 1a,25(OH)2D3 was demonstrated using the inhibitor PP2 and antisense oligodeoxynucleotides that suppress Src expression. We also observed that PI3K participates in hormone-induced proliferation. During the early phase of C2C12 cell differentiation 1a,25(OH)2D3 also increases Akt phosphorylation and activates Src. Of relevance, Src and PI3K are involved in Akt activation and in MHC and myogenin increased expression by 1a,25(OH)2D3. Altogether, these data suggest that 1a,25(OH)2D3 upregulates Akt through Src, PI3K, and p38 MAPK to stimulate myogenesis in C2C12 cells. J. Cell. Biochem. 113: 11701181, 2012. (c) 2011 Wiley Periodicals, Inc.
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