title: Leucine alleviates dexamethasone-induced suppression of muscle protein synthesis via synergy involvement of mTOR and AMPK pathways.
abstract: Glucocorticoids (GCs) are negative muscle protein regulators that contribute to the whole-body catabolic state during stress. Mammalian target of rapamycin (mTOR)-signalling pathway, which acts as a central regulator of protein metabolism, can be activated by branched-chain amino acids (BCAA). In the present study, the effect of leucine on the suppression of protein synthesis induced by GCs and the pathway involved were investigated. In vitro experiments were conducted using cultured C2C12 myoblasts to study the effect of GCs on protein synthesis, and the involvement of mTOR pathway was investigated as well. After exposure to dexamethasone (DEX, 100 μmol/l) for 24 h, protein synthesis in muscle cells was significantly suppressed (P<0.05), the phosphorylations of mTOR, ribosomal protein S6 protein kinase 1 (p70s6k1) and eukaryotic initiation factor 4E binding protein 1 (4EBP1) were significantly reduced (P<0.05). Leucine supplementation (5 mmol/l, 10 mmol/l and 15 mmol/l) for 1 h alleviated the suppression of protein synthesis induced by DEX (P<0.05) and was accompanied with the increased phosphorylation of mTOR and decreased phosphorylation of AMPK (P<0.05). Branched-chain amino transferase 2 (BCAT2) mRNA level was not influenced by DEX (P>0.05) but was increased by leucine supplementation at a dose of 5 mmol/l (P<0.05).
authors.affiliation: Department of Animal Science, Shandong Agricultural University, Taian, Shandong 271018, P.R. China.
authors.forename: Xiao J
authors.initials: XJ
authors.lastname: Wang
authors.affiliation: Department of Animal Science, Shandong Agricultural University, Taian, Shandong 271018, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Animal Science, Shandong Agricultural University, Taian, Shandong 271018, P.R. China.
authors.forename: Ru X
authors.initials: RX
authors.lastname: Wang
authors.affiliation: Department of Animal Science, Shandong Agricultural University, Taian, Shandong 271018, P.R. China.
authors.forename: Hong C
authors.initials: HC
authors.lastname: Jiao
authors.affiliation: Department of Animal Science, Shandong Agricultural University, Taian, Shandong 271018, P.R. China.
authors.forename: Jing P
authors.initials: JP
authors.lastname: Zhao
authors.affiliation: Department of Animal Science, Shandong Agricultural University, Taian, Shandong 271018, P.R. China.
authors.forename: Zhi G
authors.initials: ZG
authors.lastname: Song
authors.affiliation: Department of Animal Science, Shandong Agricultural University, Taian, Shandong 271018, P.R. China hailin@sdau.edu.cn.
authors.forename: Hai
authors.initials: H
authors.lastname: Lin
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D007930:Leucine / Q000494:pharmacology*; D051379:Mice; D009124:Muscle Proteins / Q000378:metabolism*; D032446:Myoblasts / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D014176:Protein Biosynthesis / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D005938:Glucocorticoids; D009124:Muscle Proteins; D003907:Dexamethasone; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D007930:Leucine
keywords: AMPK; glucocorticoid; leucine; mTOR; muscle cell; protein synthesis