Exercise intensity-dependent regulation of peroxisome proliferator-activated receptor. coactivator-1α mRNA abundance is associated with differential activation of upstream signalling kinases in human skeletal muscle
Exercise intensity-dependent regulation of peroxisome proliferator-activated receptor. coactivator-1α mRNA abundance is associated with differential activation of upstream signalling kinases in human skeletal muscle
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DOI：
10.1113/jphysiol.2010.188011
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发表时间：
2010-05-15
影响因子：
5.5
通讯作者：
O'Gorman, Donal J.
中科院分区：
文献类型：
--
作者：
Egan, Brendan;Carson, Brian P.;O'Gorman, Donal J.
骨骼肌收缩增加细胞内ATP周转、钙流和机械应力，启动调节过氧化物酶体增殖物激活受体的信号转导途径。辅激活因子-1a（PGC-1a）依赖的转录程序。本研究的目的是确定运动强度是否调节人类骨骼肌中PGC-1a的表达，这与已知调节PGC-1a转录的信号级联反应的激活一致。8名久坐不动的男性花费400千卡（1674千焦），在一个单一的回合的自行车测力计运动在两个不同的场合在40%（LO）或80%（HI）的。V O2 peak.骨骼肌活检。分别于运动后0、3、19 h取股外侧肌，观察股外侧肌收缩情况。两组运动时能量消耗相似，但高强度组持续时间较短（LO，69.9 ± 4.0min; HI，36.0 ± 2.2min，P < 0.05），糖原利用率较高（P < 0.05）。运动后3 h，PGC-1a mRNA丰度呈强度依赖性增加（LO，3.8倍; HI，10.2倍，P < 0.05）。HI后即刻，AMP活化蛋白激酶（AMPK）（2.8倍，P < 0.05）和钙/钙调素依赖性蛋白激酶II（CaMKII）磷酸化（84%，P < 0.05）增加，但LO则没有。p38丝裂原活化蛋白激酶（MAPK）磷酸化在两次试验后均增加（相似于2.0倍，P < 0.05），但下游转录因子激活转录因子-2（ATF-2）的磷酸化仅在HI后增加（2.4倍，P < 0.05）。两次试验后+ 3 h，cAMP反应元件结合蛋白（CREB）磷酸化水平均升高（相似于80%，P < 0.05），而IIa类组蛋白脱乙酰酶（HDAC）磷酸化水平仅在HI后升高（2.0倍，P < 0.05）。总之，运动强度调节PGC-1a mRNA丰度在人类骨骼肌响应于一个单一的回合的运动。这种效应是由多种信号通路的差异激活介导的，ATF-2和HDAC磷酸化被认为是关键的强度依赖性介质。
Skeletal muscle contraction increases intracellular ATP turnover, calcium flux, and mechanical stress, initiating signal transduction pathways that modulate peroxisome proliferator-activated receptor. coactivator-1a (PGC-1a)-dependent transcriptional programmes. The purpose of this study was to determine if the intensity of exercise regulates PGC-1a expression in human skeletal muscle, coincident with activation of signalling cascades known to regulate PGC-1a transcription. Eight sedentary males expended 400 kcal (1674 kj) during a single bout of cycle ergometer exercise on two separate occasions at either 40% (LO) or 80% (HI) of. V O2peak. Skeletal muscle biopsies from the m. vastus lateralis were taken at rest and at + 0, + 3 and + 19 h after exercise. Energy expenditure during exercise was similar between trials, but the high intensity bout was shorter in duration (LO, 69.9 +/- 4.0min; HI, 36.0 +/- 2.2min, P < 0.05) and had a higher rate of glycogen utilization (P < 0.05). PGC-1a mRNA abundance increased in an intensity-dependent manner + 3 h after exercise (LO, 3.8-fold; HI, 10.2-fold, P < 0.05). AMP-activated protein kinase (AMPK) (2.8-fold, P < 0.05) and calcium/calmodulin-dependent protein kinase II (CaMKII) phosphorylation (84%, P < 0.05) increased immediately after HI but not LO. p38 mitogen-activated protein kinase (MAPK) phosphorylation increased after both trials (similar to 2.0-fold, P < 0.05), but phosphorylation of the downstream transcription factor, activating transcription factor-2 (ATF-2), increased only after HI (2.4-fold, P < 0.05). Cyclic-AMP response element binding protein (CREB) phosphorylation was elevated at + 3 h after both trials (similar to 80%, P < 0.05) and class IIa histone deacetylase (HDAC) phosphorylation increased only after HI (2.0-fold, P < 0.05). In conclusion, exercise intensity regulates PGC-1a mRNA abundance in human skeletal muscle in response to a single bout of exercise. This effect is mediated by differential activation of multiple signalling pathways, with ATF-2 and HDAC phosphorylation proposed as key intensity-dependent mediators.