细胞外信号调节激酶在缓激肽引起血管平滑肌细胞增殖反应中的调节作用

Regulation of ERKs in Bradykinin-Induced Proliferation for Vascular Smooth Muscle Cells

目的 :本研究主要从细胞外信号调节激酶 (ERKs)的角度 ,研究丝裂原活化蛋白激酶 (MAPK)信号途径在缓激肽 (BK)介导的大鼠血管平滑肌细胞 (VSMC)促增殖等反应中的作用及其可能的调控机制。方法 :通过3H 胸苷 ( 3H TdR)掺入率与SMC3H 亮氨酸掺入率分别反映SMC的DNA代谢与蛋白质合成代谢速率 ;并通过给予MAPK激酶 (MEK )特异性抑制剂PD0 980 5 9及ERKS抑制剂UO12 6预处理 ,观察它们对细胞蛋白合成和DNA代谢及细胞增殖的影响。结果 :①BK( 10 - 8mmol/L)处理 3 0minVSMC3H 胸苷掺入率和3H 亮氨酸掺入率均明显增高 ;②BK增高3H 胸苷掺入的作用可明显被PD0 980 5 9所抑制和部分被UO12 6所抑制 ;③BK增高3H 亮氨酸掺入的作用可部分被PD0 980 5 9和UO12 6所抑制。结论 :ERKs激活在缓激肽导致VSMC增殖反应中具有重要作用 ,并可通过ERKs信号途径的特异性抑制剂的抑制效应 。

Objective: To probe into the role of extracellular signal-regulated mitogen-activated protein kinase (ERKs) on bradykinin-induced rat VSMC.Method: The DNA synthesis ratio were quantified by 3H thymidine incorporation. The protein synthesis ratio were quantified by 3H leucine incorporation. Regulation of ERKs in bradykinin-induced proliferation were investigated by preincubation with either PD98059 or U0126.Results: The results indicate that Bradykinin(10 -8 mmol/L) significantly increased 3H thymidine incorporation and 3H incorporation.Preincubation of VSMC with either PD98059 or U0126 significantly inhibited increasation of 3H thymidine incorporation induced by BK and partly inhibited increasation of 3H leucine incorporation induced by BK.Conclusion: The activation of ERKs plays an important role in VSMC growth and proliferation induced by BK.