维生素E琥珀酸酯诱导白血病细胞凋亡的信号传导机制探讨

Signal transduction mechanism in Vitamin E succinate-induced cell apoptosis in lymphoid leukemia cell

目的观察维生素E琥珀酸酯(VES)对人白血病Raji细胞的Bcl-2基因蛋白家族及JNK信号通路的作用,探讨VES诱导白血病细胞凋亡的信号传导网络调控的分子生物学机制。方法应用免疫细胞化学方法、Western免疫印迹法等技术方法,体外观察VES对Raji细胞的作用。结果VES作用后,细胞内磷酸化型JNK蛋白于6 h开始增高,12 h达到高峰,并持续24 h,而非磷酸化型JNK蛋白表达无显著变化。VES作用24 h后,细胞内Bcl-2蛋白表达下降,Bax蛋白表达增加。结论VES是JNK的激活因子,活化的JNK可能进一步通过打破促凋亡因子Bax蛋白与抗凋亡因子Bcl-2蛋白之间的平衡而启动细胞凋亡的级联反应,导致细胞凋亡。

Objective To explore the roles of apoptosis-related proteins-Bcl-2 and Bax,c-Jun N-terminal kinase in the signal transducfion of VES - induced cell apoptosis in lymphoid leukemia cell. Methods Immunocytochemical staining and Western Blotting analysis were used to observe the effects of VES in vitro. Results The level of phosphorylated form of JNK increased at 6 h and reached peak level at 12 h, and continued through 24 h after treatment in Raji cells treated with VES. The level of phosphorylation state- independent JNK did not changed. Immunocytochemical staining demonstrated that the expression of Bcl- 2 was down- regulated, while the expression of Bax increased in Raji cells treated with VES after 24 h. Conclusion VES is a potent activator of JNK, which initiates cell apoptosis by breaking the balance of Bcl - 2 and Bax .