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[目的]探讨c-Jun氨基末端激酶(JNK)信号通路在二甲基胂酸(DMA)所致人胚肺成纤维(HELF)细胞DNA损伤与凋亡中的作用。[方法]以0、2.5、5、10和20μmol/L DMA处理HELF细胞48h后,检测HELF细胞生长、DNA损伤、细胞凋亡、JNK磷酸化水平;并用20μmol/L JNK抑制剂SP600125预处理30min后,再用DMA处理HELF细胞48h,观察上述指标变化情况。[结果]10和20μmol/L DMA对HELF细胞生长产生明显抑制作用(P<0.05);2.5、5、10和20μmol/L DMA引起HELF细胞γ-H2AX表达水平明显增强(P<0.05),并具有一定剂量-效应关系(经直线相关分析,r=0.982,P<0.05);5、10和20μmol/L DMA引起HELF细胞断裂,caspase3表达水平明显增强(P<0.05),呈一定剂量-效应关系(经直线相关分析,r=0.945,P<0.05);5、10和20μmol/L DMA处理HELF细胞48h后,JNK磷酸化的表达水平明显增加(P<0.05),呈现一定剂量-效应关系(经直线相关分析,r=0.988,P<0.05);JNK抑制剂SP600125能明显降低10、20μmol/L DMA的生长抑制作用(P<0.05);JNK抑制剂SP600125可明显阻滞DMA所致HELF细胞对DNA损伤和诱导的凋亡作用(P<0.05)。[结论]DMA可引起HELF细胞DNA损伤和凋亡;在此过程中JNK信号通路激活起到正调控作用。
[Objective] To investigate the effect of c-Jun N-terminal kinase (JNK) signaling pathway on DNA damage and apoptosis induced by dimethylarsinic acid (DMA) in human embryo lung fibroblasts (HELF). [Methods] The HELF cells were treated with 0, 2.5, 5, 10, 10 and 20μmol / L DMA for 48h. The growth, DNA damage, apoptosis and JNK phosphorylation of HELF cells were detected by HEK293 cells and pretreated with 20μmol / L JNK inhibitor SP600125 After that, HELF cells were treated with DMA for 48 hours again to observe the changes of these indexes. [Results] 10 and 20 μmol / L DMA significantly inhibited the growth of HELF cells (P <0.05). The expression of γ-H2AX in HELF cells was significantly enhanced by 2.5, 5, 10 and 20 μmol / L DMA (R = 0.982, P <0.05); 5, 10 and 20 μmol / L DMA caused the cleavage of HELF cells and the increased expression of caspase 3 (P <0.05), showing a dose-response relationship (R = 0.945, P <0.05). After treatment with 5, 10 and 20 μmol / L DMA for 48 h, the expression of JNK phosphorylation increased significantly (P <0.05), showing a dose-response relationship (P <0.05); JNK inhibitor SP600125 can significantly reduce the growth inhibition of 10,20μmol / L DMA (P <0.05); JNK inhibitor SP600125 can significantly block the effect of DMA induced HELF DNA damage and apoptosis induced by cells (P <0.05). [Conclusion] DMA can cause DNA damage and apoptosis in HELF cells. The activation of JNK signaling pathway plays a positive regulatory role in this process.