Insight into skeletal muscle mechanotransduction: MAPK activation is quantitatively related to tension
Insight into skeletal muscle mechanotransduction: MAPK activation is quantitatively related to tension
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DOI：
10.1152/jappl.2001.91.2.693
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发表时间：
2001-08-01
影响因子：
3.3
通讯作者：
Gardiner, PF
中科院分区：
文献类型：
--
作者：
Martineau, LC;Gardiner, PF
机械力通过骨骼肌细胞产生细胞内信号的机制，称为机械转导，以及基因表达和细胞大小如何通过这种信号调节的细节知之甚少。已知有丝分裂原活化蛋白激酶（MAPKs）参与各种细胞类型中机械诱导的信号传导，包括骨骼肌，据报道骨骼肌中的MAPK激活是对收缩和被动牵拉的反应。因此，研究骨骼肌在机械应力下的MAPK激活可能会产生有关机械转导过程的重要信息。与使用大鼠足底原位制备，广泛的峰值张力产生通过被动拉伸和同心，等距，偏心收缩协议，和c-Jun氨基末端激酶（JNK），细胞外调节激酶（ERK），和p38 MAPK的磷酸化进行了评估。JNK和ERK MAPK的亚型被发现以张力依赖的方式磷酸化，使得偏心。等距的同心的被动拉伸峰值张力被认为是一个更好的预测MAPK磷酸化比时间-张力积分或张力发展率。JNK和ERK MAPK之间最大反应幅度和敏感性的差异表明这两个激酶家族在机械诱导信号传导中的不同作用。观察到p54 JNK磷酸化和峰值张力之间在15倍张力范围内的强线性关系（r（2）= 0.89，n = 32），支持收缩类型差异可以用张力来解释的事实，并证明MAPK激活是施加于肌肉的机械应力大小的定量反映。因此，MAPK活化的测量，作为骨骼肌机械转导的测定，可能有助于阐明机械诱导的肥大。
The mechanism by which mechanical forces acting through skeletal muscle cells generate intracellular signaling, known as mechanotransduction, and the details of how gene expression and cell size are regulated by this signaling are poorly understood. Mitogen-activated protein kinases (MAPKs) are known to be involved in mechanically induced signaling in various cell types, including skeletal muscle where MAPK activation has been reported in response to contraction and passive stretch. Therefore, the investigation of MAPK activation in response to mechanical stress in skeletal muscle may yield important information about the mechanotransduction process. With the use of a rat plantaris in situ preparation, a wide range of peak tensions was generated through passive stretch and concentric, isometric, and eccentric contractile protocols, and the resulting phosphorylation of c-Jun NH2-terminal kinase (JNK), extracellular regulated kinase (ERK), and p38 MAPKs was assessed. Isoforms of JNK and ERK MAPKs were found to be phosphorylated in a tension-dependent manner, such that eccentric. isometric. concentric. passive stretch. Peak tension was found to be a better predictor of MAPK phosphorylation than time-tension integral or rate of tension development. Differences in maximal response amplitude and sensitivity between JNK and ERK MAPKs suggest different roles for these two kinase families in mechanically induced signaling. A strong linear relationship between p54 JNK phosphorylation and peak tension over a 15-fold range in tension (r(2) = 0.89, n = 32) was observed, supporting the fact that contraction-type differences can be explained in terms of tension and demonstrating that MAPK activation is a quantitative reflection of the magnitude of mechanical stress applied to muscle. Thus the measurement of MAPK activation, as an assay of skeletal muscle mechanotransduction, may help elucidate mechanically induced hypertrophy.