Molecular mechanism of enhanced apoptotic response in U937 cells mediated by sodium butyrate
Zhou, J.; Tang, Y.; Liu, W.; Sun, H.; Hu, J.; Gong, J.
Zhonghua Zhong Liu Za Zhi 24(4): 320-322
2002
ISSN/ISBN: 0253-3766 PMID: 12408754 Document Number: 541343
Objective: To study the effects of sodium butyrate (NaBu) on cell cycle checkpoint and the apoptosis sensitivity in U937 cells. Methods: 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. Results: U937-pZeosv2(+) pretreated with NaBu exhibited enhanced apoptotic response in a NaBu dose dependent fashion upon 137Cs 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. Conclusion: NaBu is able to enhance the apoptotic response in U937 cells, which is mediated by p38 MAPK activation but not ATM status.