皮质酮快速激活PC12细胞中p38丝列原激活的蛋白激酶
李晓煜, 邱俭, 肖林, 朱剑琴, 陈宜张
南京大学生物科学与技术系.江苏,南京 210093;第二军医大学神经科学研究所.上海 200433;第二军医大学生理学教研室.上海 200433
摘要
实验旨在研究糖皮质激素快速、非基因组作用的细胞内信号传导机制。Western分析研究结果表明,皮质酮可快速激活PC12细胞中p38丝列原激活的蛋白激酶(mitogen-activated protein kinase,MAPK),时间、浓度曲线均为钟形,最大激活为10~(-9) mol/L和15min。糖皮质激素受体阻断剂RU38486不能阻断此作用,而小牛血清白蛋白耦联的皮质酮也能快速激活p38。受体酪氨酸激酶阻断剂genistein对此作用无影响,表明此快速作用不涉及受体酪氨酸激酶活性。此作用能被蛋白激酶C(protein kinase C,PKC)激动剂PMA模拟,而被PKC阻断剂Go6976所阻断。结果表明,皮质酮可能通过推测的膜受体以PKC依赖的方式快速激活p38 MAPK。
关键词: 皮质酮; 非基因组作用; p38; 蛋白激酶C; PC12
Rapid activation of p38 mitogen-activated protein kinase by corticosterone in PC12 cells
Li Xiaoyu, Qiu Jian, Xiao Lin, Zhu Jianqin, Chen Yizhang
Department of Biological Science and Technology,Nanjing University.Nanjing 210093,Jiangsu;China;Department of Physiology,Second Military Medical University.Shanghai 200433
Abstract
The present study using immunoblot showed that corticosterone (B) could induce a rapid activation of p38 in PC12 cells. The dose- and time-response curves were bell-shaped with a maximal activation at 10~(-9)mol/L and 15 min respectively. The activation was not affected by steroid nuclear receptor antagonist RU38486. Bovine serum albumin coupled B (B-BSA) could induce phosphorylation of p38. Tyrosine kinase inhibitor genistein failed to block the phosphorylation, a fact suggesting that the tyrosine kinase activity is not involved in the pathway. On the other hand, phorbol 12-myristate 13-acetate (PMA), a protein kinase C (PKC) activator, could mimic the actions of B, while Goo6976, a PKC inhibitor, could completely abolish the phosphorylation induced by B. These results clearly demonstrate that B activates p38 MAPK readily via a putative membrane receptor through a PKC-dependent pathway.
Key words: Corticosterone;Nongenomication;p38;Protein kinase C(PKC);PC12 cells
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引用本文:
李晓煜, 邱俭, 肖林, 朱剑琴, 陈宜张. 皮质酮快速激活PC12细胞中p38丝列原激活的蛋白激酶[J]. 生理学报 2001; 53 (6): .
Li Xiaoyu, Qiu Jian, Xiao Lin, Zhu Jianqin, Chen Yizhang. Rapid activation of p38 mitogen-activated protein kinase by corticosterone in PC12 cells. Acta Physiol Sin 2001; 53 (6): (in Chinese with English abstract).