AMPK inhibits myoblast differentiation through a PGC-1α-dependent mechanism

• DOI: 10.1152/ajpendo.91007.2008
• Publication Date: 2009-06-02T21:31:10Z
• Authors: David L. Williamson; David C. Butler; Stephen E. Alway
• Keywords: AMP-Activated Protein Kinase

Elevated phosphorylation of AMP-activated protein kinase (AMPK) has been shown to inhibit skeletal muscle growth in both culture and animal models, but its role differentiation cells is less clear. p21 known have an important differentiation, AMPK's regulating cultures unknown. Therefore, the purpose this study was determine under conditions elevated AMPK phosphorylation. Treating C(2)C(12) myoblast with 1 mM 5-aminoimidazole-4-carboxamide 1-beta-D-ribonucleoside (AICAR) for up 24 h induced Activation reduced mRNA expression, which associated G(1)/S cell cycle transition promoter activity. AICAR-treated myoblasts undergoing also had myotube formation, myosin accumulation. When were treated AICAR h, p21, MyoD significantly reduced. Myotube atrophy apparent compared control conditions. Addition compound C, inhibitor, attenuated AICAR's negative effects on cultures. The nuclear expression appeared be more affected by myotubes than cytosolic portion protein, C treatment. Further analysis revealed that treatment increased PGC-1alpha decreased FOXO3A reversed cotreatment. Knockdown shRNA corroborated data, preserving expression. These data demonstrate AICAR-induced inhibits transition, reducing into myotubes, through PGC-1alpha-FOXO3A-p21.