title: Insulin-like growth factor-1 (IGF-1) and leucine activate pig myogenic satellite cells through mammalian target of rapamycin (mTOR) pathway.
abstract: 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.
authors.affiliation: College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, People's Republic of China.
authors.forename: Bing
authors.initials: B
authors.lastname: Han
authors.forename: Junfeng
authors.initials: J
authors.lastname: Tong
authors.forename: Mei J
authors.initials: MJ
authors.lastname: Zhu
authors.forename: Changwei
authors.initials: C
authors.lastname: Ma
authors.forename: Min
authors.initials: M
authors.lastname: Du
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D053687:Adult Stem Cells / Q000166:cytology / Q000201:enzymology*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology*; D007930:Leucine / Q000378:metabolism / Q000494:pharmacology; D018482:Muscle, Skeletal / Q000166:cytology / Q000201:enzymology*; D014176:Protein Biosynthesis / Q000187:drug effects / Q000502:physiology; D011494:Protein Kinases / Q000378:metabolism*; D019893:Ribosomal Protein S6 Kinases / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D020123:Sirolimus / Q000494:pharmacology; D013552:Swine; D058570:TOR Serine-Threonine Kinases; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000903:Antibiotics, Antineoplastic; D007334:Insulin-Like Growth Factor I; D011494:Protein Kinases; D019893:Ribosomal Protein S6 Kinases; D058570:TOR Serine-Threonine Kinases; D007930:Leucine; D020123:Sirolimus