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This Article Full Text Full Text (PDF) All Versions of this Article: 92/1/207    most recent expphysiol.2006.034736v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Niesler, C. U. Articles by Moore, F. Search for Related Content PubMed PubMed Citation Articles by Niesler, C. U. Articles by Moore, F.

¹ Department of Physiological Sciences, University of Stellenbosch, Private Bag X1, Stellenbosch 7602, South Africa

AMP-activated protein kinase (AMPK) functions as a /ß/ heterotrimer to preserve ATP levels and so cell viability during stressful conditions. However, its role in aiding survival of adult skeletal muscle precursor cells is unclear. Using the differentiating mouse C2C12 postnatal skeletal muscle myoblast cell line, we have determined that proteins for the AMPK subunit isoforms 2 and 2 are constitutively expressed, while those for 1, ß1 and ß2 are undetectable in undifferentiated myoblasts but increasingly expressed with differentiation to myotubes. Although the 3 subunit is expressed at a low level in myoblasts, it too is expressed increasingly with differentiation to myotubes. The p50 but not the p72 isoform of the embryonic subunit homologue MELK is expressed only in proliferating myoblasts, while the ARK5 subunit homologue is increasingly expressed with differentiation. Myotubes displayed higher basal and stimulated 1/2 AMPK activation than myoblasts. Furthermore, serum starvation resulted in less apoptosis of differentiated myotubes than of undifferentiated myoblasts. This reflects, in part, the increased expression of functional AMPK in the myotubes, since specific inhibition of AMPK activity with 6-[4-(2-piperidin-1-ylethoxy)-phenyl]-3-pyridin-4-ylpyrazolo[1,5-] pyrimidine (Compound C) exacerbated the apoptosis resulting from serum withdrawal. If these in vitro events can also occur in vivo, they could have implications for pathologies such as muscle wasting, in which undifferentiated satellite stem cells may be easier apoptotic targets than their differentiated counterparts. Furthermore, these results suggest that when interpreting results from in vitro or in vivo experiments on AMPK, the subunit expression profile should be taken into account.

(Received 20 June 2006; accepted after revision 29 August 2006; first published online 31 August 2006)
Corresponding author F. Moore: Hormone and Metabolic Research Unit, Christian de Duve Institute of Cellular Pathology, University of Louvain Medical School, ICP-UCL 7529, Avenue Hippocrate 75, B-1200 Brussels, Belgium. Email: frances.moore{at}horm.ucl.ac.be