三丁基锡对人羊膜细胞ERK通路和G2/M期调控蛋白的影响  

The effects of tributyltin on ERK cascades and G2 /M regulators in human amnionic cells

作　　者：张亚莉[1] 徐立红[2] 

机构地区：[1]南通大学医学院生物化学与分子生物学教研室,江苏南通226001 [2]浙江大学医学院生物化学与遗传学系

出　　处：《毒理学杂志》2014年第2期104-108,共5页Journal of Toxicology

基　　金：国家自然科学基金(20777067);江苏省自然科学青年基金(BK20130397);南通大学博士引进人才启动基金(13R26)

摘　　要：目的研究三丁基锡(Tributyltin,TBT)对正常人羊膜FL细胞ERK通路及周期相关蛋白的影响。方法 FL细胞分别以剂量1、2、3、4和6μmol/L TBT染毒,免疫印迹法检测ERK通路和周期蛋白表达及磷酸化水平的变化。结果 TBT下调Raf表达,促使下游激酶MEK1/2,ERK1/2以及转录因子c-Myc脱磷酸后失活,抑制ERK通路;同时细胞周期磷酸酶Cdc25C表达下调,激酶Cdc2 Tyr-15位点磷酸化水平升高。结论 ERK通路的抑制可能是TBT发挥细胞毒性作用的重要因素,其机制主要是通过调控Cdc25C,致使G2/M关键激酶Cdc2活性下调,细胞发生G2/M期阻滞,最终诱导凋亡。Objective To investigate the effects of tributyltin （TBT） on extracellular signal-regulated kinase （ERK） cascades and some key regulators in the G2/M phase in human amnionic cells. Methods FL cells were treated with TBT at the concentration of 1, 2, 3, 4 and 6 μmol/L. ERK cascades that involves c-Raf, MEK1/2 and c-Myc, and some key regulators in the G2/M phase, such as Cdc25C and Cdc2, respectively, were examined by western blotting. Results The results showed TBT inhibited ERK cascade by deceasing c-Raf, then dephosphorylating MEK1/2, ERK1/2, as well as c-Myc. Additionally, TBT induced downregulation of total Cdc25C levels and increase of phospho-Cdc2. Conclusion Therefore, ERK cascades inhibition might be a key mediator of TBT toxicity and may trigger apoptosis via the decease of total Cdc25C protein and consequent increase in the phospho-Cdc2.

关 键 词：三丁基锡 ERK通路 Cdc25C CDC2 

分 类 号：R114[医药卫生—卫生毒理学]