Immediate response of mammalian target of rapamycin (mTOR)-mediated signalling following acute resistance exercise in rat skeletal muscle

被引:184
作者
Bolster, DR
Kubica, N
Crozier, SJ
Williamson, DL
Farrell, PA
Kimball, SR
Jefferson, LS
机构
[1] Penn State Univ, Coll Med, Dept Cellular & Mol Physiol, Hershey, PA 17033 USA
[2] Penn State Univ, Noll Physiol Res Ctr, University Pk, PA 16802 USA
[3] Penn State Univ, Grad Program Physiol, University Pk, PA 16802 USA
来源
JOURNAL OF PHYSIOLOGY-LONDON | 2003年 / 553卷 / 01期
关键词
D O I
10.1113/jphysiol.2003.047019
中图分类号
Q189 [神经科学];
学科分类号
071006 [神经生物学];
摘要
The purpose of the present investigation was to determine whether mammalian target of rapamycin (mTOR)-mediated signalling and some key regulatory proteins of translation initiation are altered in skeletal muscle during the immediate phase of recovery following acute resistance exercise. Rats were operantly conditioned to reach an illuminated bar located high on a Plexiglass cage, such that the animals completed concentric and eccentric contractions involving the hindlimb musculature. Gastrocnemius muscle was extracted immediately after acute exercise and 5, 10, 15, 30 and 60 min of recovery. Phosphorylation of protein kinase B (PKB) on Ser-473 peaked at 10 min of recovery (282% of control, P < 0.05) with no significant changes noted for mTOR phosphorylation on Ser-2448. Eukaryotic initiation factor (eIF) 4E-binding protein-1 (4E-BP1) and S6 kinase-1 (SW1), both downstream effectors of mTOR, were altered during recovery as well. 4E-BP1 phosphorylation was significantly elevated at 10 min (292%, P < 0.01) of recovery. S6K1 phosphorylation on Thr-389 demonstrated a trend for peak activation at 10 min following exercise (336%, P = 0.06) with ribosomal protein S6 phosphorylation being maximally activated at 15 min of recovery (647%, P < 0.05). Components of the eIF4F complex were enhanced during recovery as eIF4E association with eIF4G peaked at 10 min (292%, P < 0.05). Events regulating the binding of initiator methionyl-tRNA to the 40S ribosomal subunit were assessed through eIF2B activity and eIF2alpha phosphorylation on Ser-51. No differences were noted with either eIF2B or eIF2alpha. Collectively, these results provide strong evidence that mTOR-mediating signalling is transiently upregulated during the immediate period following resistance exercise and this response may constitute the most proximal growth response of the cell.
引用
收藏
页码:213 / 220
页数:8
相关论文
共 42 条
[1]
Mechanism of activation of protein kinase B by insulin and IGF-1 [J].
Alessi, DR ;
Andjelkovic, M ;
Caudwell, B ;
Cron, P ;
Morrice, N ;
Cohen, P ;
Hemmings, BA .
EMBO JOURNAL, 1996, 15 (23) :6541-6551
[2]
Phosphorylation of p70S6k correlates with increased skeletal muscle mass following resistance exercise [J].
Baar, K ;
Esser, K .
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 1999, 276 (01) :C120-C127
[3]
PHYSIOLOGICAL HYPERINSULINEMIA STIMULATES PROTEIN-SYNTHESIS AND ENHANCES TRANSPORT OF SELECTED AMINO-ACIDS IN HUMAN SKELETAL-MUSCLE [J].
BIOLO, G ;
FLEMING, RYD ;
WOLFE, RR .
JOURNAL OF CLINICAL INVESTIGATION, 1995, 95 (02) :811-819
[4]
Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo [J].
Bodine, SC ;
Stitt, TN ;
Gonzalez, M ;
Kline, WO ;
Stover, GL ;
Bauerlein, R ;
Zlotchenko, E ;
Scrimgeour, A ;
Lawrence, JC ;
Glass, DJ ;
Yancopoulos, GD .
NATURE CELL BIOLOGY, 2001, 3 (11) :1014-1019
[5]
RAFT1 phosphorylation of the translational regulators p70 S6 kinase and 4E-BP1 [J].
Burnett, PE ;
Barrow, RK ;
Cohen, NA ;
Snyder, SH ;
Sabatini, DM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (04) :1432-1437
[6]
CHANGES IN HUMAN MUSCLE PROTEIN-SYNTHESIS AFTER RESISTANCE EXERCISE [J].
CHESLEY, A ;
MACDOUGALL, JD ;
TARNOPOLSKY, MA ;
ATKINSON, SA ;
SMITH, K .
JOURNAL OF APPLIED PHYSIOLOGY, 1992, 73 (04) :1383-1388
[7]
COLEMAN CS, 1993, J BIOL CHEM, V268, P24572
[8]
Eukaryotic initiation factors and protein synthesis after resistance exercise in rats [J].
Farrell, PA ;
Hernandez, JM ;
Fedele, MJ ;
Vary, TC ;
Kimball, SR ;
Jefferson, LS .
JOURNAL OF APPLIED PHYSIOLOGY, 2000, 88 (03) :1036-1042
[9]
Regulation of protein synthesis after acute resistance exercise in diabetic rats [J].
Farrell, PA ;
Fedele, MJ ;
Vary, TC ;
Kimball, SR ;
Lang, CH ;
Jefferson, LS .
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 1999, 276 (04) :E721-E727
[10]
PANCREATIC-ISLET INSULIN-SECRETION IS INCREASED AFTER RESISTANCE EXERCISE IN RATS [J].
FLUCKEY, JD ;
KRAEMER, WJ ;
FARRELL, PA .
JOURNAL OF APPLIED PHYSIOLOGY, 1995, 79 (04) :1100-1105