三丁基锡对蛋白磷酸酶2A的抑制机制

Inhibition mechanism of TBT to PP2A activity in human amnionic cells

目的研究三丁基锡(TBT)对人羊膜FL细胞蛋白磷酸酶2A(PP2A)活力的抑制机制。方法 FL细胞经不同浓度TBT染毒1 h后,检测PP2A活力及PP2A组成亚基A、C、B55α和B56δ以及C亚基蛋白磷酸化和甲基化水平。结果与对照组比较,3、4、6μmol/L染毒FL细胞内PP2A活力均下降,差异有统计学意义(P<0.01);6μmol/L TBT染毒组FL细胞内PP2A组成亚基A蛋白的表达下降,4、6μmol/L TBT染毒组B55α蛋白的表达及C蛋白甲基化水平均降低,差异有统计学意义(P<0.05)。结论 TBT对FL细胞PP2A活力的抑制作用可能与其抑制B55α和A蛋白亚基表达,降低C亚基Leu309位点的甲基化水平有关。

Objective To investigate the inhibition mechanism of tributyltin（TBT） on protein phosphatase 2A（PP2A） activity in human amnionic FL cells. Methods 1 h after contamination by different concentrations of TBT,FL cells were detected on the PP2A activity,levels of PP2A subunits including A,C,B55αand B56δ,protein phosphorylation of C and methylation level. Results Compared with control group,the activity of PP2A in FL cells was declined when the concentration was in 3,4 and 6μmol/L in TBT groups with statistically significant difference（P〈0.01）;PP2A-A subunit was decreased in 6μmol/L TBT group, and B55αsubunit and the methylation of PP2A-C were significantly decreased in the 4μmol/L and 6μmol/L TBT groups,the dif ferences all had statistically significant differnce（P〈0.05）. Conclusion The inhibitory effect of IBT to PP2A in FL cells may be associated with modifications of B55αand A subunit and reduction of PP2A-C methylation in Leu309 area.