p38MAPK基因敲除对亚砷酸盐诱导细胞凋亡的影响  

Effects of p38 MAPK gene knockout on arsenite-induced cell apoptosis

作　　者：刘爱华[1] 龚小卫[2] 魏洁[2] 明小燕[2] 王达安[2] 邓鹏[2] 罗深秋[3] 姜勇[2] 

机构地区：[1]南方医科大学南方医院呼吸科,广东广州510515 [2]南方医科大学病理生理学教研室和广东省蛋白质组学重点实验室,广东广州510515 [3]南方医科大学细胞生物学教研室,广东广州510515

出　　处：《中国病理生理杂志》2008年第5期892-895,共4页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.30572151);国家自然科学基金委员会-广东省人民政府自然科学联合基金重点资助项目(No.U0632004);广东省自然科学基金资助项目(No.05004730)

摘　　要：目的:研究p38丝裂原活化蛋白激酶(MAPK)在应激刺激诱导的细胞凋亡中的作用。方法:p38+/+和p38-/-细胞用NaAsO2刺激后,用多聚甲醛固定及DAPI染核,利用荧光显微镜观察细胞核的形态改变。NaAsO2刺激的p38+/+和p38-/-细胞用Annexin V-FITC与PI双标后,用流式细胞分析仪分析细胞凋亡百分率。结果:NaAsO2刺激后,大部分p38-/-细胞产生典型的凋亡细胞形态学变化,p38+/+细胞仅少数细胞出现核固缩。而且,p38-/-细胞中凋亡细胞百分率较刺激前和p38+/+细胞都显著增加,而p38+/+细胞的凋亡率没有明显变化。结论:p38基因敲除使细胞对亚砷酸盐应激刺激的耐受性下降,容易发生凋亡;p38丝裂原活化蛋白激酶可能在提高细胞的应激适应能力上发挥着重要的作用。AIM： To investigate the role of p38 mitogen - activated protein kinase （MAPK） in the cell apoptosis induced by arsenite. METHODS： After the treatment with or without arsenite, p^38＋/＋ and p38^-/- cells were fixed with paraformaldehyde and stained with DAPI. The nuclear morphological changes were observed under a fluorescence microscope, p38^＋/＋ and p38^-/- cells were double-stained with Annexin V-FITC and PI, and the ratios of apoptotic cells were detected by flow cytometry. RESULTS ： With the stimulation of arsenite, typical apoptotic morphological changes appeared in most p38^-/- cells, yet only a few p38^＋/＋ cells showed nucleus condensation. Consistently, the ratio of apoptotic p38^-/- cells induced by arsenite significantly increased in comparison with that in the untreated cells （P 〈0.01 ）, and also much higher than that in p38^＋/＋ cells stimulated with arsenite （P 〈 0. 01 ）. CONCLUSION： p38 gene knockout leads to a decrease in cellular resistance to stress of arsenite, which produces a proapoptotic state, p38 MAPK may play an important role on the enhancement of cell adaptive capability to harmful stresses.

关 键 词：p38 MAP激酶 基因敲除 细胞凋亡 应激 亚砷酸盐类 

分 类 号：Q25[生物学—细胞生物学]