JNK、ERK信号通路在NaAsO_2诱导骨髓间充质干细胞增殖中的作用

目的：研究c-jnk氨基末端激酶（JNK）、细胞外信号调节激酶（ERK）在亚砷酸钠（NaAs02）诱导骨髓间充质干细胞（BMSC）增殖中的作用。方法：体外培养骨髓间充质干细胞,四甲基偶氮唑盐比色法（MTT法）检测细胞增殖,Western-blot检测磷酸化JNK、ERK表达水平。结果：低浓度1、2μmol/LNaAs02对BMSC有明显的促进增殖作用;高浓度16、32μmol/LNaAs02则对细胞生长产生抑制作用,具有一定剂量-效应关系;2、4、8μmol/LNaAs02处理BMSC24h后,JNK磷酸化表达水平明显增加,ERK磷酸化表达水平明显降低;JNK抑制剂SP600125可明显降低高浓度16、32μmol/LNaAs02的生长抑制作用;ERK抑制剂PD98059可抑制低浓度1、2μmol/LNaAs02对BMSC的促增殖作用。结论：低浓度NaAs02激活ERK信号通路,提高细胞增殖率,可被抑制剂PD98059阻断;高浓度NaAs02激活JNK信号通路,提高细胞凋亡率,可被抑制剂SP600125阻断。NaAs02致癌机制可能与JNK、ERK信号通路作用相关。

Effects of JNK ERK signaling pathway in proliferation of bone marrow mesenchymal stem cells induced by NaAsO_2

Objective：To study the effects of c-jnk N-terminal kinase（JNK）,extracellular signal-regulated kinase（ERK） in the sodium arsenite（NaAs02）-induced on cell proliferation in bone marrow mesenchymal stem cells（BMSC）.Method：bone marrow mesenchymal stem cells were cultured in vitro,cell proliferation were detected by MTT,Western-blot detection of the expression levels of phosphor-JNK and phosphor-ERK.Result：the levels of proliferation were significantly increased with low concentration of 1,2 μmol /L NaAs02 in BMSC;high concentrations of 16,32 μmol /L NaAs02 on cell growth was inhibited,the indices with a dose-effect relatio nship;After BMSC were treated with control,2,4 and 8 μmol /L NaAs02 for 24h,the expression levels of phosphor-JNK were significantly increased,the expression levels of phosphor-ERK were significantly lower ;JNK inhibitor,SP600125 could significantly reduce the cell proliferation with high concentration of 16,32 μmol /L NaAs02;ERK inhibitor PD98059 inhibited the low concentration of 1,2μmol /L NaAs02 right-promoting BMSC proliferation.Conclusion：low concentration of NaAs02 activated ERK signaling pathway to enhance cell proliferation rate,can be inhibitor PD98059 blocked;high concentrations of NaAs02 activated JNK signaling pathway to enhance the rate of apoptosis may be blocked inhibitor SP600125.NaAs02 carcinogenic mechanism may be related to JNK,ERK signaling pathway-related role.