Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2001-11

AUTHORS

Sue C. Bodine, Trevor N. Stitt, Michael Gonzalez, William O. Kline, Gretchen L. Stover, Roy Bauerlein, Elizabeth Zlotchenko, Angus Scrimgeour, John C. Lawrence, David J. Glass, George D. Yancopoulos

ABSTRACT

Skeletal muscles adapt to changes in their workload by regulating fibre size by unknown mechanisms. The roles of two signalling pathways implicated in muscle hypertrophy on the basis of findings in vitro, Akt/mTOR (mammalian target of rapamycin) and calcineurin/NFAT (nuclear factor of activated T cells), were investigated in several models of skeletal muscle hypertrophy and atrophy in vivo. The Akt/mTOR pathway was upregulated during hypertrophy and downregulated during muscle atrophy. Furthermore, rapamycin, a selective blocker of mTOR, blocked hypertrophy in all models tested, without causing atrophy in control muscles. In contrast, the calcineurin pathway was not activated during hypertrophy in vivo, and inhibitors of calcineurin, cyclosporin A and FK506 did not blunt hypertrophy. Finally, genetic activation of the Akt/mTOR pathway was sufficient to cause hypertrophy and prevent atrophy in vivo, whereas genetic blockade of this pathway blocked hypertrophy in vivo. We conclude that the activation of the Akt/mTOR pathway and its downstream targets, p70S6K and PHAS-1/4E-BP1, is requisitely involved in regulating skeletal muscle fibre size, and that activation of the Akt/mTOR pathway can oppose muscle atrophy induced by disuse. More... »

PAGES

1014

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ncb1101-1014

DOI

http://dx.doi.org/10.1038/ncb1101-1014

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1045639258

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/11715023


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N-Triples is a line-based linked data format ideal for batch operations.

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Turtle is a human-readable linked data format.

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RDF/XML is a standard XML format for linked data.

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