Effects Of Jnk And Erk1/2 Signaling Pathway Induced By Sodium Arsenite In Bone Marrow Mesenchymal Stem Cells

Objective:To study the proliferation and apoptosis of bone marrow mesenchymal stem cells (BMSCs) of mice incubated with different concentrations of sodium arsenite (NaAsO2) for different time respectively, and to discuss the effects of c-jnk N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK1/2) in the proliferation and apoptosis of BMSCs..Method:The bone marrow mesenchymal stem cells were incubated with different concentrations of NaAsO2 for 24,48h respectively, MTT assay was used to measure cell proliferation. Cells apoptosis were confirmed by FACS. BMSCs were infected by different concentrations of NaAsO2 for 24h, Western-blot detection of the expression levels of JNK, ERK1/2, ph-JNK, p- ERK1/2; BMSCs pretreatmented with JNK inhibitor SP600125, ERK1/2 inhibitor PD98059 30min were treated with different concentrations of NaAsO2 for 24,48h respectively, MTT assay was used to measure cell proliferation; The cells apoptosis were confirmed by FACS.Results:(1) The proliferation of BMSC were promoted by NaAsO2 less than 2μmol/L (p>0.05); When the concentration of NaAsO2 increased more than 8μmol/L, it inhibited cell proliferation (p<0.01), the proliferation inhibition rate increased in dose-time fashion. (2) The expression of phosphor- JNK of BMSCs infected by NaAsO2 for 24h was markedly enhanced along with the increasing of concentration of NaAsO2 and was the strongest in 8μmol/L NaAsO2(p<0.05). The expression of phosphor- ERK1/2 of BMSCs was significantly decreased with the concentration of NaAsO2, and it is stronger in 2,4μmol/L NaAsO2 and tit was significantly down in 8μmol/L (p<0.05). (3) The cell proliferation inhibition rate of BMScs remarkably decreased by JNK inhibitor SP600125 in 16,32μmol/L NaAsO2 respectively (p< 0.05); The proliferation of BMSCs was inhibited by ERK1/2 inhibitor PD98059 in the 1,2μmol/L NaAsO2 respectively (p<0.05). (4) The apoptosis rate of BMSCs,infected by different concentration of NaAsO2 for 24,48h respectively, were increased,by JNK inhibitor in a dose -time fashion and it does its best in 4μmol/L NaAsO2 (p<0.05); apoptosis rate of BMSCs was increased by ERK1/2 inhibitor and a large number of cell debris were observed in 8μmol/L NaAsO2 (p<0.05).Conclusion:Biphasic effects of proliferation and apoptosis of BMSCs were induced by different concentration of NaAsO2 respectively. JNK, ERK1/2 signaling pathway may be involved in the mechanism of NaAsO2 acted on BMSCs.