Altered PKC expression and phosphorylation in response to the nature, direction, and magnitude of mechanical stretch.
Altered PKC expression and phosphorylation in response to the nature, direction, and magnitude of mechanical stretch.
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根据机械拉伸的性质、方向和幅度改变 PKC 表达和磷酸化。
DOI：
10.1139/y07-023
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发表时间：
2007
影响因子：
2.1
通讯作者：
Price,RobertL
中科院分区：
文献类型：
--
作者：
Bullard,TaraA;Hastings,JoshuaL;Davis,JeffreyM;Borg,ThomasK;Price,RobertL
蛋白激酶C （PKC）同工酶已被证明在多种细胞类型的机械转导中发挥作用。我们试图通过检查蛋白表达和磷酸化的变化来确定PKC同工酶参与转导机械（循环与静态）、方向和强度的拉伸。我们使用了一种三维培养系统，将新生大鼠心肌细胞排列在硅橡胶膜上。肌细胞以5周期/分钟的速度进行循环拉伸，或以0%、2.5%、5%或10%的强度进行24小时的静态拉伸。拉伸应用于垂直或平行方向的肌细胞排列。PKC δ对垂直于肌细胞排列的拉伸最敏感，无论拉伸的性质如何，而磷酸化PKC δ T505对静态垂直拉伸的响应增加。循环拉伸改变PKC ε表达，静态拉伸不改变，而磷酸化PKC ε S719表达不变。拉伸未改变PKC α的表达；然而，磷酸化PKC α S657在周期垂直拉伸后呈剂量依赖性增加。我们的研究结果表明PKC表达和磷酸化状态的变化可能是心肌细胞区分机械拉伸的性质、方向和强度的一种机制。
Protein kinase C (PKC) isozymes have been shown to play a role in mechanotransduction in a variety of cell types. We sought to identify the PKC isozymes involved in transducing mechanical (cyclic vs. static), direction and intensity of stretch by examining changes in protein expression and phosphorylation. We used a 3-dimensional culture system with aligned neonatal rat cardiac myocytes on silastic membranes. Myocytes were subjected to either cyclic stretch at 5 cycles/min or static stretch for a period of 24 h at intensities of 0%, 2.5%, 5%, or 10% of full membrane length. Stretch was applied in perpendicular or parallel directions to myocyte alignment. PKC δ was most sensitive to stretch applied perpendicular to myocyte alignment regardless of the nature of stretch, while phospho PKC δ T505 increased in response to static-perpendicular stretch. PKC ε expression was altered by cyclic stretch but not static stretch, while phospho PKC ε S719 remained unchanged. PKC α expression was not altered by stretch; however, phospho PKC α S657 increased in a dose-dependent manner following cyclic-perpendicular stretch. Our results indicate that changes in PKC expression and phosphorylation state may be a mechanism for cardiac myocytes to discriminate between the nature, direction, and intensity of mechanical stretch.