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Tyrosine kinase-mediated activation of NADPH oxidase enhances proliferative capacity of diabetic vascular smooth muscle cells.

机译:酪氨酸激酶介导的NADPH氧化酶的激活增强了糖尿病血管平滑肌细胞的增殖能力。

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摘要

To investigate a potential molecular basis for a link between diabetes and atherosclerosis, experiments were performed to determine the role of NADPH oxidase in the enhanced proliferative capacity of vascular smooth muscle cells (VSMC) from OLETF rat, an animal model of type 2 diabetes. An enhanced proliferative response to 10% fetal bovine serum with an increased cell cycle progression from G1 to S phase as well as an augmented superoxide generation with an increased NADPH oxidase activity were observed in diabetic versus control VSMC. Both the enhanced proliferation and superoxide generation in diabetic VSMC were significantly attenuated not only by diphenyleneiodonium (10 microM) and apocynin (100 microM), NADPH oxidase inhibitors but also by protein tyrosine kinase inhibitors such as genistein (100 microM) and AG 112 (100 microM). Furthermore, the enhanced NADPH oxidase activity in diabetic VSMC was significantly attenuated by genistein and AG112, but not by daidzein (100 microM), a genistein analogue devoid of protein tyrosine kinase inhibitory properties. Based on these results, it is suggested that the enhanced proliferative capacity of diabetic VSMC is closely related to the activation of NADPH oxidase that is induced through activation of protein tyrosine kinase.
机译:为了研究糖尿病与动脉粥样硬化之间联系的潜在分子基础,进行了实验以确定NADPH氧化酶在OLETF大鼠(一种2型糖尿病动物模型)的血管平滑肌细胞(VSMC)增殖能力增强中的作用。在糖尿病与对照VSMC中,观察到对10%胎牛血清的增殖反应增强,细胞周期从G1期增加到S期,以及超氧化物生成增加,NADPH氧化酶活性增加。糖尿病VSMC中增强的增殖和超氧化物的产生不仅被二苯撑碘铵(10 microM)和载脂蛋白(100 microM),NADPH氧化酶抑制剂显着减弱,而且还被蛋白酪氨酸激酶抑制剂如金雀异黄素(100 microM)和AG 112(100 microM)。此外,染料木黄酮和AG112显着减弱了糖尿病VSMC中增强的NADPH氧化酶活性,但黄豆苷元(100 microM)则没有,而黄豆苷元(一种没有蛋白质酪氨酸激酶抑制特性的染料木黄酮类似物)则没有。基于这些结果,表明糖尿病性VSMC的增强的增殖能力与通过蛋白酪氨酸激酶的激活诱导的NADPH氧化酶的激活密切相关。

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