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Involvement of PI3K/Akt/TOR pathway in stretch‐induced hypertrophy of myotubes
Author(s) -
Sasai Nobuaki,
Agata Nobuhide,
InoueMiyazu Masumi,
Kawakami Keisuke,
Kobayashi Kunihiko,
Sokabe Masahiro,
Hayakawa Kimihide
Publication year - 2010
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.21473
Subject(s) - wortmannin , protein kinase b , myogenesis , pi3k/akt/mtor pathway , muscle hypertrophy , mapk/erk pathway , microbiology and biotechnology , kinase , phosphorylation , signal transduction , myocyte , chemistry , skeletal muscle , mek inhibitor , medicine , endocrinology , biology
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. Muscle Nerve, 2010