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JNK/SAPK信号转导通路在镉引起的Hormesis中的作用
The effect of JNK/SAPK signal transduction on hormesis induced by cadmium
【摘要】 目的研究重金属镉对Hek293细胞的低剂量兴奋效应及JNK/SAPK信号转导通路在其中所起的作用。方法以0,1.0,3.0,9.0,27.0μmol/L浓度的氯化镉(CdCl2)染毒Hek293细胞24和36 h;在研究JNK/SAPK信号转导通路特异性抑制剂作用时,在染毒前先用SP600125预处理1 h。用MTT法测定细胞的增殖。用Western Blot方法检测磷酸化JNK/SAPK蛋白水平的变化。结果1.0μmol/L剂量的CdCl2染毒Hek293细胞24和36 h,其增殖率与对照组相比分别升高了9.96%和33.3%,差异均具有统计学意义,加入SP600125后,与对照组相比增殖率没有明显的升高;而在3.0μmol/L剂量以上染毒浓度时,增殖率随剂量增加而降低。1.0,3.0μmol/L剂量CdCl2作用于Hek293细胞对磷酸化JNK蛋白无明显影响,高于3.0μmol/L剂量时可以使JNK蛋白持续磷酸化激活至少12 h。当加入SP600125后,以上变化趋势不受影响。结论低剂量CdCl2作用于Hek293细胞可以引起Hormesis效应,该效应可以被JNK/SAPK信号转导通路特异性抑制剂SP600125阻断。JNK/SAPK信号转导通路对Hormesis效应的影响可能主要是JNK蛋白下游转录因子的作用。
【Abstract】 Objective To study the hormesis of low-dose cadmium on Hek293 cell and the possible effect of JNK/SAPK signal transduction involved.Methods Hek293 cell was treated with cadmium of 0,1.0,3.0,9.0,27.0 μmol/L for 24 h or 36 h.While study the effect of the special inhibitor on JNK/SAPK signal transduction,SP600125 was added before the cell was treated with cadmium.The proliferation viability was measured by the thiazolyl blue(MTT) assay.The effect of JNK/SAPK signal transduction on the hormesis was evaluated by examining the level of the phosphorylated-JNK/SAPK,using the western blot method.Results Compared with the control group,the growth rate of Hek293 cell increased 9.96% and 33.3% respectively after treated with 1.0 μmol/L cadmium for 24 h and 36 h.When added the special inhibitor of the JNK/SAPK signal transduction,ie.SP600125,the growth rate did not markedly change at the dose of 1.0 μmol/L.When treated with cadmium with the dose above 3.0 μmol/L,the growth rate decreased obviously,also in the groups of adding SP600125.After treated with cadmium for 2,4 or 12 h,the phosphor-JNK/SAPK of Hek293 cell did not show significant differences below the 3.0 μmol/L dose groups,but raised in the groups of above 3.0 μmol/L compared with the control group.The special inhibitor of JNK/SAPK SP600125 did not have an obvious influence on the phosphorylation of the JNK/SAPK.Conclusion The Hek293 cell showed obvious hormesis effect after treated with 1.0 μmol/L cadmium for 24 or 36 h,but the effect disappeared when the special inhibitor of JNK/SAPK SP600125 was added.It was probably that the transcription factors activated by phosphor-JNK/SAPK contributed to the hormesis effect.
【Key words】 Cadmium; Hormesis; Hek293 Cell; Proliferation; JNK/SAPK cell signaling transduction;
- 【文献出处】 毒理学杂志 ,Journal of Toxicology , 编辑部邮箱 ,2007年03期
- 【分类号】R114
- 【被引频次】8
- 【下载频次】367