过氧化氢预处理对抗氧化应激诱导的PC12细胞凋亡(英文)  

Hydrogen peroxide preconditioning protects PC12 cells against apoptosis induced by oxidative stress

作　　者：唐小卿[1] 陈静[1] 唐二虎[1] 冯鉴强[1] 陈培熹[1] 

机构地区：[1]中山大学中山医学院生理学教研室

出　　处：《生理学报》2005年第2期211-216,共6页Acta Physiologica Sinica

基　　金：This work was supported by the Natural Science Foundation of Guangdong Province (No. 001322).

摘　　要：氧化应激可明显地诱导细胞凋亡。本研究旨在探讨H2O2。预处理能否对H2O2诱导的PC12细胞凋亡产生保护作用及ATP 敏感性K+(ATP-sensitive potassium,KATP)通道在其中的作用。采用PI染色流式细胞仪(flow cytometry,FCM)检测PC12细胞凋亡。结果表明,经10 μmol/L H2O2预处理90 min的PC12细胞,分别在20、30、50和100 μmol/L H2O2作用24 h后,其细胞凋亡率明显下降,与未经H2O2预处理的PC12细胞相比,差异极显著(P<0.01),表明H2O2预处理对H2O2诱导PC12细胞凋亡具有保护作用。用10μmol/L的KATP通道激动剂pinacidil(Pin)可显著减少30和50μmol/L H2O2诱导的PC12细胞凋亡,10 μmol/L的KATP通道拮抗剂glybenclamide(Gly)则可显著地抑制甚至取消KATP通道激动剂Pin对H2O2诱导PC12细胞凋亡的保护作用,但并不影响H2O2预处理对H2O2诱导PC12细胞凋亡的保护作用;然而,当联合应用H2O2预处理与Pin时,对PC12 细胞凋亡的保护作用明显大于各自的抗凋亡作用。提示KATP通道开放不仅对H2O2诱导PC12细胞凋亡具有保护作用,而且与H2O2预处理一起产生抗PC12细胞凋亡的协同作用,但KATP通道开放可能不参与H2O2预处理的适应性保护作用。Oxidative stress can induce significant cell death by apoptosis. We explore whether prior exposure to H2O2 (H2O2 preconditioning) protects PC12 cells against the apoptotic consequences of subsequent oxidative damages and what role the ATP-sensitive potassium (KATP) channels play in the preconditioning protection. PC12 cells were preconditioned with 90 min exposure to H2O2 at 10 μmol/L, followed by 24-h recovery and subsequent exposures to different concentrations (20, 30, 50 and 100 μmol/L) of H2O2for 24 h respectively. We used PI staining flow cytometry (FCM) to observe the apoptosis of PC12 cells. It was shown that 24-h exposures to H2O2 at 20, 30, 50 and 100 μmol/L respectively induced substantial cell apoptosis, which was greatly prevented in the preconditioning cells, indicating that H2O2 preconditioning protected PC12 cells against apoptosis induced by H2O2. Administration of pinacidil (10 μmol/L), an KATP channel activator, significantly attenuated the apoptosis of PC12 cells induced by H2O2 at 30 and 50 μmol/L for 24 h respectively. Glybenclamide (10μmol/L), a KATP channel inhibitor, significantly suppressed or abolished the protective effects caused by the pinacidil but not by H2O2 preconditioning. However, when both H2O2 preconditioning and pinacidil were co-applied, their protection against the apoptosis of PC12 cells was much stronger than that of the individual one of them. These results suggest that H2O2 preconditioning protects PC12 cells against apoptosis and that the activation of KATP channels is not involved in, but synergetically enhances adaptive protection of H2O2 preconditioning.

关 键 词：预处理 H2O2 PC12细胞 凋亡 ATP-敏感性钾通道 

分 类 号：Q255[生物学—细胞生物学]