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Insulin‐like growth factor‐1 (IGF‐1) and leucine activate pig myogenic satellite cells through mammalian target of rapamycin (mTOR) pathway
Author(s) -
Han Bing,
Tong Junfeng,
Zhu Mei J.,
Ma Changwei,
Du Min
Publication year - 2008
Publication title -
molecular reproduction and development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 105
eISSN - 1098-2795
pISSN - 1040-452X
DOI - 10.1002/mrd.20832
Subject(s) - pi3k/akt/mtor pathway , rptor , biology , microbiology and biotechnology , leucine , phosphorylation , mechanistic target of rapamycin , insulin like growth factor , protein kinase b , signal transduction , growth factor , mtorc2 , mtorc1 , cell growth , medicine , biochemistry , receptor , amino acid
Myogenic satellite cells are adult stem cells and have important roles in skeletal muscle growth, repair, and regeneration. Both insulin‐like growth factor‐1 (IGF‐1) and leucine stimulate skeletal muscle growth, which link to the activation and proliferation of myogenic satellite cells in skeletal muscle. Mammalian target of rapamycin (mTOR) signaling is one of the main signaling pathways controlling protein synthesis and cell proliferation. Thus, IGF‐1 and leucine may stimulate activation of myogenic satellite cells through mTOR signaling. In this study, myogenic satellite cells were isolated from 6‐month‐old pigs and subjected to IGF‐1 and leucine treatments. Both IGF‐1 and leucine upregulated mTOR signaling in myogenic satellite cells. The phosphorylation of mTOR at Ser 2448 increased 83.8 ± 7.7% by IGF‐1 ( P < 0.05) and 83.4 ± 5.7% by leucine ( P < 0.05). The downstream targets of mTOR, S6 kinase, and 4E‐binding protein 1 (4EBP1) were also phosphorylated due to IGF‐1 and leucine treatments. Treatment with IGF‐1 and leucine induced the phosphorylation of tuburin (TSC2), a key mediator upstream of mTOR signaling, by 272.8 ± 26.4% and 94.2 ± 28.7%, respectively. Treatment of cells with both IGF‐1 and leucine did not show synergistic effect on mTOR signaling. Inhibition of mTOR by rapamycin abolished the protein synthesis and cell proliferation stimulated by both IGF‐1 and leucine. In summary, our data showed that in preliminary cultured myogenic satellite cells mTOR signaling was activated due to IGF‐1 and leucine treatments, and this mTOR activation is necessary for the activation of myogenic satellite cells. Mol. Reprod. Dev. 75: 810–817, 2008. © 2007 Wiley‐Liss, Inc.