Marathon running transiently increases c-Jun NH2-terminal kinase and p38γ activities in human skeletal muscle
Marathon running transiently increases c-Jun NH2-terminal kinase and p38γ activities in human skeletal muscle
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DOI：
10.1111/j.1469-7793.2000.00663.x
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发表时间：
2000-08-01
影响因子：
5.5
通讯作者：
Goodyear, LJ
中科院分区：
文献类型：
--
作者：
Boppart, MD;Asp, S;Goodyear, LJ
1. 我们研究了应激激活蛋白激酶信号分子c-Jun NH、末端激酶（JNK）和p38激酶在长时间剧烈跑步运动下骨骼肌中的激活和失活模式。男性受试者(n = 14，年龄32 +/- 2岁，V-O2,V-max 60 +/- 2 ml kg（-1) min(-1)）完成42.2 km马拉松（平均比赛时间3小时35分钟）。肌肉活组织检查分别在马拉松赛前10天、赛后1天、3天和5天进行。用免疫复合物法检测JNK和p38（包括p38 α和p38 γ）的活化，用磷酸化特异性抗体评估p38 （α和γ）以及JNK和p38的上游调节因子，丝裂原活化蛋白激酶4 （MKK4）和丝裂原活化蛋白激酶6 （MKK6）的磷酸化状态。物。运动后活动量比基础水平增加了7倍，但在运动后1、3和5天降回基础水平。P38 γ磷酸化（4倍）和活性（1.5倍）在运动后立即增加，并在运动后1、3和5天恢复到基础水平。相比之下，p38a的磷酸化和活性在研究的时间过程中没有变化。MKK4和MKK6磷酸化的上升和下降趋势与JNK活性和p38 γ磷酸化相似。长时间的跑步运动并不影响JNK、p38 α和p38 γ蛋白在比赛后几天的表达。这项研究表明，JNK和p38细胞内信号级联在长时间的跑步运动后都是稳定的，但会短暂地增加。人类骨骼肌中p38亚型随着运动的不同激活表明这些蛋白在体内可能具有不同的功能。
1. We examined the: pattern of activation and deactivation of the stress-activated protein kinase signalling molecules c-Jun NH,-terminal kinase (JNK) and p38 kinase in skeletal muscle in response to prolonged strenuous running exercise in human subjects.2.Male subjects (n = 14; age 32 +/- 2 years; V-O2,V-max 60 +/- 2 ml kg(-1) min(-1)) completed a 42.2 km marathon (mean race time 3 h 35 min). Muscle biopsies were obtained 10 days prior to the marathon, immediattely following the race, and 1, 3 and 5 days after the race. The activation of JNK and p38, including both p38 alpha and p38 gamma, was measured with immune complex assays, The phosphorylation state of p38 (alpha and gamma) and the upstream regulators of JNK and p38, mitogen-activated protein kinase kinase 4 (MKK4) and mitogen-activated protein kinase kinase 6 (MKK6), were assessed using phosphospecific antibodies.3. JNK. activity increased 7-fold over basal level immediately post-exercise, but decreased back to basal levels 1, 3 and 5 days after the exercise. p38 gamma phosphorylation (4-fold) and activity (1.5-fold) increased immediately post-exercise and returned to basal levels at 1, 3 and 5 days following exercise. In contrast, p38a phosphorylation and activity did not change over the time course studied. MKK4 and MKK6 phosphorylation increased and decreased in a trend similar to that observed with JNK activity and p38 gamma phosphorylation. Prolonged running exercise did not affect JNK, p38 alpha, or p38 gamma protein expression in the days following the race.4. This study demonstrates that both JNK and p38 intracellular signalling cascades are robustly, yet transiently increased following prolonged running exercise, The differential activation of title p38 isoforms with exercise in human skeletal muscle indicates that these proteins may have distinct functions in vivo.