Involvement of PI3K/Akt/TOR pathway in stretch-induced hypertrophy of myotubes.

Abstract:

:Skeletal muscle cells are hypertrophied by mechanical stresses, but the underlying molecular mechanisms are not fully understood. Two signaling pathways, phosphatidylinositol 3-kinase (PI3K)/Akt to target of rapamycin (TOR) and extracellular signal-regulated kinase kinase (MEK) to extracellular signal-regulated kinase (ERK), have been proposed to be involved in muscle hypertrophy. In this study we examined the involvement of these pathways in primary cultures of chick skeletal myotubes subjected to passive cyclic stretching for 72 hours, a time that was sufficient to induce significant hypertrophy in our preparations. Hypertrophy was largely suppressed by wortmannin or rapamycin, inhibitors of PI3K or mTOR, respectively. Furthermore, phosphorylation of Akt was enhanced by stretching and suppressed by wortmannin. The MEK inhibitor, U0126, exerted a minimal influence on stretch-induced hypertrophy. We found that cyclic stretching of myotubes activates the PI3K/Akt/TOR pathway, resulting in muscle hypertrophy. The MEK/ERK pathway may contribute negatively to spontaneous hypertrophy.

journal_name

Muscle Nerve

journal_title

Muscle & nerve

authors

Sasai N,Agata N,Inoue-Miyazu M,Kawakami K,Kobayashi K,Sokabe M,Hayakawa K

doi

10.1002/mus.21473

subject

Has Abstract

pub_date

2010-01-01 00:00:00

pages

100-6

issue

1

eissn

0148-639X

issn

1097-4598

journal_volume

41

pub_type

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