Zhou Jianfeng, Tang Yi, Liu Wenli, Sun Hanying, Hu Junbo, Gong Jianping
Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430030, China.
Zhonghua Zhong Liu Za Zhi. 2002 Jul;24(4):320-2.
To study the effects of sodium butyrate (NaBu) on cell cycle checkpoint and the apoptosis sensitivity in U937 cells.
Two mutant U937 cell lines, U937-ASPI3K (ATM negative) and U937-pZeosv2(+) (ATM wild-type), were used as the cell model system. Immunoprecipitation and kinase assay were used to examine the p38 MAPK and ERK1 kinase activities. Western blot was used to analyze the phosphorylation of Bad protein.
U937-pZeosv2(+) pretreated with NaBu exhibited enhanced apoptotic response in a NaBu dose dependent fashion upon (137)Cs irradiation, which could be abolished by olomoucine (OLM), a p38 MAPK specific inhibitor. On the other hand, Cyclin dependent kinase 2 (CDK2) specific inhibitor CDK2-I and p34cdc2/cyclinB inhibitor alsterpaullone (ALP) failed to block the effects of NaBu. Similar results were also observed in U937-ASPI3K. The effect of irradiation on p38 MAPK and ERK1 was strikingly potentiated by NaBu. Furthermore, inactivation of irradiated Bad protein via phosphorylation on serine 136 was also enhanced.
NaBu is able to enhance the apoptotic response in U937 cells, which is mediated by p38 MAPK activation but not ATM status.
研究丁酸钠（NaBu）对U937细胞周期检查点及凋亡敏感性的影响。
使用两种突变的U937细胞系，U937-ASPI3K（ATM阴性）和U937-pZeosv2(+)（ATM野生型）作为细胞模型系统。采用免疫沉淀和激酶测定法检测p38丝裂原活化蛋白激酶（MAPK）和细胞外信号调节激酶1（ERK1）的激酶活性。使用蛋白质印迹法分析Bad蛋白的磷酸化情况。
用NaBu预处理的U937-pZeosv2(+)在受到(137)Cs照射后，以NaBu剂量依赖性方式表现出增强的凋亡反应，该反应可被p38 MAPK特异性抑制剂olomoucine（OLM）消除。另一方面，细胞周期蛋白依赖性激酶2（CDK2）特异性抑制剂CDK2-I和p34cdc2/细胞周期蛋白B抑制剂alsterpaullone（ALP）未能阻断NaBu的作用。在U937-ASPI3K中也观察到了类似结果。NaBu显著增强了照射对p38 MAPK和ERK1的作用。此外，经丝氨酸136磷酸化使照射后的Bad蛋白失活的情况也得到增强。
NaBu能够增强U937细胞的凋亡反应，这是由p38 MAPK激活介导的，而非ATM状态。
