ERK1／2-STAT3通路在H2O2预处理导致的适应性细胞保护中的作用  

Role of ERK1/2-STAT3 pathway in adaptive cytoprotection induced by H_2O_2 preconditioning

作　　者：廖新学[1] 王艳丽[2] 郭瑞鲜[2] 孙胜楠[2] 胡芬[2] 陈培熹[2] 冯鉴强[2] 

机构地区：[1]中山大学中山医学院生理教研室,广东广州510080

出　　处：《中国病理生理杂志》2008年第9期1839-1844,共6页Chinese Journal of Pathophysiology

基　　金：广东省科技计划项目(No.2006B60501024,No.2004B30601016,No.2007B080701030);广东省自然科学基金资助项目(No.5001676)

摘　　要：目的:探讨ERK1/2-STAT3通路在H2O2预处理导致的适应性细胞保护中的作用。方法:在PC12细胞建立H2O2预处理对抗氧化应激(300μmol/L H2O2)损伤细胞的模型。应用Hoechst33258核染色法观察细胞调亡的形态学改变;应用碘化丙啶(PI)染色流式细胞术检测细胞凋亡率;免疫印记法(Western blotting)测定p-ERK1/2和p-STAT3的表达水平。结果:100μmol/L H2O2预处理PC12细胞90 min可明显抑制300μmol/LH2O2作用12 h引起的细胞凋亡,并激活ERK1/2和STAT3;ERK1/2抑制剂UO126和JAK2抑制剂AG-490(10μmol/L)均可明显地阻断H2O2预处理引起的细胞保护作用;UO126(10μmol/L)亦能明显地抑制H2O2预处理对STAT3的上调作用。结论:H2O2预处理能激活PC12细胞的ERK1/2-STAT3信号转导旁路,这可能是预处理的细胞保护机制之一。AIM： To explore the role of extracellular signal - regulated kinases ERK1/2 - STAT3 pathway in adaptive cytoproteetion induced by H2O2 preconditioning in PC12 cells. METHODS： In PC12 cells, the experimental model of cytoprotection by H2O2 preconditioning against oxidative stress - induced injury was set up. The morphological changes in the apoptotic cells were observed by using of chromatin dye Hoechst 33258. The percent of apoptotic cells was determined by flow cytometry （ FCM ） with propidium iodide staining. The levels of p - ERK1/2 and p - STAT3 expression were detected by Western blotting assay. RESULTS： Preconditioning with H2O2 at concentration of 100 μmol/L for 90 min obviously inhibited apoptosis induced by 300 μmol/L H2O2, and both ERK1/2 and STAT3 were activated. UO126 （ 10 μmol/L, an inhibitor of ERK1/2） or AG -490 （ 10μmol/L, an inhibitor of JAK2） significantly blocked the cytoprotection effect of H2O2 preconditioning. Moreover, UO126 （10 μmol/L） also markedly inhibited the up- regulation of pSTAT3 expression by H2O2 preconditioning. CONCLUSION： H2O2 preconditioning activates ERK1/2 -STAT3 signal pathway, which may be one of the mechanisms underlying H2O2 preconditioninginduced cytoprotection.

关 键 词：ERK1/2通路 STAT3通路 过氧化氢 预处理 适应性细胞保护 

分 类 号：R-338.2[医药卫生]