血管紧张素 II 通过 PI3K/ Akt/FOXO1 信号通路诱导骨骼肌细胞萎缩.

Objective To investigate the regulation and mechanism of angiotensin II (Ang II) on skeletal muscle cells. Methods C2C12 myoblasts were divided into three groups(Control, Ang II and Ang II+ ARB) according to their treatment with Ang II or Olmesartan. 2% horse serum was used to induce myoblasts differentiated into myotubes. Myotubes average area were detected by immunofluorescence staining, and Western blot was used to test the changes in protein expressions of muscle-specific ubiquitin ligases, myogenic regulatory factors (MRFs) and PI3K / Akt / FOXO1 signaling pathway. Results Immunofluorescence staining showed that the average diameter and area of myotubes decreased after Ang II treatment (P <0. 001) and these phenotypes of myotubes could be markedly reversed (P <0. 01) by Ang II type 1 receptor, olmesartan. Additionally, the protein level of the muscle?specific ubiquitin ligases including MURF1 (P<0. 05) and MAFbx (P<0. 001) were up-regulated induced by Ang II, while the ratio of p?PI3K / PI3K (P<0. 01), p-Akt / Akt (P<0. 001) and p-FOXO1/ FOXO1 (P<0. 01) as well as MRFs including MHC (P<0. 01) and MyoD (P<0. 05) were down?regulaed, and Olmesartan treatment could attenuate the effect of Ang II on myotube proteins. Conclusion Ang II can promote protein degradation and inhibit protein synthesis to induce muscle cell atrophy by inhibiting the phosphorylation of PI3K / Akt / FOXO1 signaling pathway. [ABSTRACT FROM AUTHOR]