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目的:研究咖啡因对磷酸肌醇-3-激酶抑制剂诱导的小脑颗粒神经元凋亡的作用及机制。方法:神经元体外培养,凝胶电泳,SAPK/JNK分析盒测定JNK活性。结果:LY294002浓度依赖性地触发小脑颗粒神经元凋亡,但咖啡因具有浓度依赖性的保护作用。此作用不受ryanodine-敏感性钙释放阻断剂、L-型钙通道阻断剂和NMDA受体阻断剂的影响。而且,RP-cAMP,H89和KN62均不能抑制咖啡因的保护作用。c-Jun的磷酸化是LY294002诱导神经原凋亡所必需,咖啡因可直接抑制JNK的活性,降低神经元内磷酸化c-Jun的含量。结论:咖啡因通过直接抑制JNK活性而抑制小脑颗粒神经元的凋亡。
Objective: To investigate the effect and mechanism of caffeine on apoptosis of cerebellar granule neurons induced by phosphoinositide-3-kinase inhibitor. Methods: Neurons were cultured in vitro, gel electrophoresis, and the activity of JNK was measured by SAPK / JNK assay kit. RESULTS: LY294002 triggered cerebellar granule neurons apoptosis in a concentration-dependent manner, but caffeine had a concentration-dependent protective effect. This effect is not affected by ryanodine-sensitive calcium release blockers, L-type calcium channel blockers and NMDA receptor blockers. Moreover, neither RP-cAMP nor H89 nor KN62 inhibited the protective effect of caffeine. Phosphorylation of c-Jun is necessary for LY294002 to induce neuronal apoptosis. Caffeine can directly inhibit the activity of JNK and decrease the content of phosphorylated c-Jun in neurons. Conclusion: Caffeine inhibits cerebellar granule neurons apoptosis by directly inhibiting JNK activity.