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The link between AMP-activated protein kinase (AMPK) and myogenesis remains poorly defined. AMPK has two catalytic αsubunits, α1 and α2. We postulated that AMPK promotes myogenesis in an isoform-specific manner. Primary myoblasts wereprepared from AMPK knockout (KO) mice and AMPK conditional KO mice, and knockout of the α1 but not the α2 subunit resultedin downregulation of myogenin and reduced myogenesis. Myogenin expression and myogenesis were nearly abolished inthe absence of both AMPKα1 and AMPKα2, while enhanced AMPK activity promoted myogenesis and myotube formation. TheAMPKα1-specific effect on myogenesis was likely due to the dominant expression of α1 in myoblasts. These results were confirmedin C2C12 cells. To further evaluate the necessity of the AMPKα1 subunit for myogenesis in vivo, we prepared both DsRedAMPKα1 knockout myoblasts and enhanced green fluorescent protein (EGFP) wild-type myoblasts, which were cotransplantedinto tibialis anterior muscle. A number of green fluorescent muscle fibers were observed, showing the fusion of engrafted wildtypemyoblasts with muscle fibers; on the other hand, very few or no red muscle fibers were observed, indicating the absence ofmyogenic capacity of AMPKα1 knockout myoblasts. In summary, these results indicate that AMPK activity promotes myogenesisthrough a mechanism mediated by AMPKα1. © 2013, American Society for Microbiology.

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Molecular and Cellular Biology

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