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Y27632 抑制 ROCK 可促进脊髓星形胶质细胞的增殖和细胞周期进程。

ROCK inhibition with Y27632 promotes the proliferation and cell cycle progression of cultured astrocyte from spinal cord.

机构信息

Department of Neurology, Huazhong University of Science and Technology, Wuhan, People's Republic of China.

出版信息

Neurochem Int. 2012 Dec;61(7):1114-20. doi: 10.1016/j.neuint.2012.08.003. Epub 2012 Aug 19.

Abstract

Rho-associated Kinase (ROCK) has been identified as an important regulator of proliferation and cell cycle progression in a number of cell types. Although its effects on astrocyte proliferation have not been well characterized, ROCK has been reported to play important roles in gap junction formation, morphology, and migration of astrocytes. In the present study, our aim was to investigate the effect of ROCK inhibition by [(+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl) cyclohexanecarboxamide dihydrochloride] (Y27632) on proliferation and DNA synthesis in cultured astrocytes from rat spinal cord and the possible mechanism involved. Western blots showed that treatment of astrocytes with Y27632 increased their expression of cyclin D1, CDK4, and cyclin E, thereby causing cell cycle progression. Furthermore, Y27632-induced astrocyte proliferation was mediated through the extracellular-signal-regulated kinase signaling cascade. These results indicate the importance of ROCK in astrocyte proliferation.

摘要

Rho 相关激酶(ROCK)已被确定为多种细胞类型中增殖和细胞周期进程的重要调节因子。尽管其对星形胶质细胞增殖的影响尚未得到很好的描述,但 ROCK 已被报道在缝隙连接形成、星形胶质细胞形态和迁移中发挥重要作用。在本研究中,我们的目的是研究 [(+)-(R)-trans-4-(1-氨基乙基)-N-(4-吡啶基)环己烷甲酰胺二盐酸盐](Y27632)抑制 ROCK 对大鼠脊髓星形胶质细胞增殖和 DNA 合成的影响及其可能涉及的机制。Western blot 显示,Y27632 处理星形胶质细胞可增加 cyclin D1、CDK4 和 cyclin E 的表达,从而导致细胞周期进程。此外,Y27632 诱导的星形胶质细胞增殖是通过细胞外信号调节激酶信号级联介导的。这些结果表明 ROCK 在星形胶质细胞增殖中的重要性。

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