Regulation of stretch-induced JNK activation by stress fiber orientation
Regulation of stretch-induced JNK activation by stress fiber orientation
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DOI：
10.1016/j.cellsig.2006.02.008
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发表时间：
2006-11-01
影响因子：
4.8
通讯作者：
Chien, Shu
中科院分区：
文献类型：
--
作者：
Kaunas, Roland;Usami, Shunichi;Chien, Shu
与脉动血压相关的周期性机械牵张可以调节血管内皮细胞的细胞骨架重塑和细胞内信号传导。本研究的目的是评估牵张诱导的肌动蛋白应力纤维取向在涉及牛主动脉内皮细胞c-jun N-末端激酶（INK）激活的细胞内信号传导中的作用。设计了一种能够对培养的内皮细胞施加周期性单轴和等双轴拉伸以及改变周期性单轴拉伸方向的拉伸装置。响应于10%的循环等双轴拉伸，其不导致应力纤维取向，INK活化升高达6小时。响应于10%的周期性单轴拉伸，JNK活性仅短暂升高，随后随着肌动蛋白应力纤维的取向垂直于拉伸方向而恢复到基础水平。在应力纤维垂直排列且JNK活性消退后，循环单轴拉伸方向的90度变化使JNK重新活化，并且当应力纤维垂直于新的拉伸方向重新取向时，这种活化再次消退。用细胞松弛素D破坏肌动蛋白丝阻断了应力纤维对周期性单轴拉伸的取向，也导致了单轴拉伸诱导的JNK激活变得持续。这些结果表明，应力纤维取向垂直于拉伸方向提供了一种机制，结构和生化适应循环机械拉伸。(c)2006年爱思唯尔公司All rights reserved.
Cyclic mechanical stretch associated with pulsatile blood pressure can modulate cytoskeletal remodeling and intracellular signaling in vascular endothelial cells. The aim of this study was to evaluate the role of stretch-induced actin stress fiber orientation in intracellular signaling involving the activation of c-jun N-terminal kinase (INK) in bovine aortic endothelial cells. A stretch device was designed with the capability of applying cyclic uniaxial and equibiaxial stretches to cultured endothelial cells, as well as changing the direction of cyclic uniaxial stretch. In response to 10% cyclic equibiaxial stretch, which did not result in stress fiber orientation, INK activation was elevated for up to 6 h. In response to 10% cyclic uniaxial stretch, JNK activity was only transiently elevated, followed by a return to basal level as the actin stress fibers became oriented perpendicular to the direction of stretch. After the stress fibers had aligned perpendicularly and the INK activity had subsided, a 90 degrees change in the direction of cyclic uniaxial stretch reactivated JNK, and this activation again subsided as stress fibers became re-oriented perpendicular to the new direction of stretch. Disrupting actin filaments with cytochalasin D blocked the stress fiber orientation in response to cyclic uniaxial stretch and it also caused the uniaxial stretch-induced JNK activation to become sustained. These results suggest that stress fiber orientation perpendicular to the direction of stretch provides a mechanism for both structural and biochemical adaptation to cyclic mechanical stretch. (c) 2006 Elsevier Inc. All rights reserved.