藤黄酸通过MAPK通路诱导Jurkat细胞凋亡的机理  

Gambogic Acid Induces Apoptosis of Jurkat Cell through the MAPK Signal Pathway

作　　者：徐勇[1] 欧阳建[1] 张启国[1] 周敏[1] 李娟[1] 陈敏敏[1] 徐岳一[1] 

机构地区：[1]南京中医药大学中西医结合鼓楼临床医院血液科,江苏南京210008

出　　处：《中国实验血液学杂志》2012年第3期587-591,共5页Journal of Experimental Hematology

摘　　要：本研究探讨藤黄酸对Jurkat细胞的抑制作用及可能机理。以不同浓度藤黄酸与抑制剂处理Jurkat细胞,AnnexinⅤ/PI双染法检测细胞的凋亡;流式细胞仪检测荧光素激活的caspase 3、caspase 8、caspase 9阳性细胞水平;免疫印迹检测pro-caspase 3、pro-caspase 9、磷酸化JNK及P38蛋白水平。结果表明,藤黄酸呈浓度依赖性诱导Jurkat细胞凋亡;藤黄酸作用Jurkat细胞后caspase 3、caspase 8、caspase 9阳性细胞水平升高,caspase 3、caspase 9活化蛋白及磷酸化JNK及P38蛋白水平升高;ROS、CaMKⅡ、caspase 3、caspase 9、MAPKK、JNK1/2及P38抑制剂减弱藤黄酸诱导Jurkat细胞凋亡的作用;ROS、CaMKⅡ、MAPKK、JNK1/2及P38抑制剂降低藤黄酸作用Jurkat细胞后caspase 3、caspase 9活化蛋白水平;ROS、CaMKⅡ、MAPKK、JNK1/2抑制剂降低藤黄酸作用Jurkat细胞后磷酸化JNK蛋白水平;ROS、CaMKⅡ、MAPKK、P38抑制剂减弱藤黄酸作用Jurkat细胞后磷酸化P38蛋白水平。结论:藤黄酸通过激活caspase途径诱导Jurkat细胞凋亡,该过程可能与ROS-CaMKⅡ-MAPKK-JNK/P38通路有关。The aim of this study was to investigate the apoptosis-inducing effect of gambogic acid（GA） on Jurkat cells and its underlying signaling pathway.Apoptosis induced by GA and some inhibitors was assayed by Annexin Ⅴ/PI doubling staining.The levels of caspase 3,caspase 8 and caspase 9 activated in living Jurkat cells were measured by flow cytometry.The expressions of caspase 3,caspase 9,p-JNK and P38 were detected by Western blot.The results showed that GA induced apoptosis of Jurkat cells in a dose-dependent manner.The positive cell number of activated caspase 3,caspase 8,caspase 9 and the levels of activated caspase 3,caspase 9,p-JNK,P38 increased after Jurkat cells were treated with GA.ROS,CaMKⅡ,caspase 3,caspase 9,MAPKK,JNK1/2 and P38 inhibitors had some significant effect on GA-induced apoptosis.ROS,CaMKⅡ,MAPKK,JNK1/2 and P38 inhibitors decreased the levels of activated caspase 3,caspase 9 by GA.ROS,CaMKⅡ,MAPKK,JNK1/2 inhibitors decreased the levels of p-JNK by GA.ROS,CaMKⅡ,MAPKK,P38 inhibitors decreased the levels of P38 by GA.It is concluded that GA induced apoptosis of Jurkat cells by activated caspases through activating of ROS-CaMKⅡ-MAPKK-JNK/P38 pathway.

关 键 词：藤黄酸 CASPASES 凋亡 JURKAT细胞 MAPK通路 

分 类 号：R733.7[医药卫生—肿瘤] R979.1[医药卫生—临床医学]