BDE-47对人胚肾细胞HEK293的毒理效应及作用机制

2,2’,4,4’-四溴联苯醚(BDE-47)是生物体中含量最高且毒性最强的PBDEs之一,有关BDE-47对肾细胞的毒性及其作用机制的研究仍有待补充。选取3个剂量组(低:10-6mol·L-1、中:10-5mol·L-1、高:10-4mol·L-1)及溶剂对照组,研究了BDE-47对人胚肾细胞(HEK293)的细胞凋亡率及活性氧(ROS)水平的影响;并从分子水平对细胞氧化损伤、凋亡相关蛋白(APE1及p53)及凋亡相关基因m RNA(p53、Bax、Caspase 3、Caspase 8)的表达量进行测定。实验结果显示:与对照组相比,中、高剂量组细胞凋亡率显著增加(P0.05);ROS水平在中剂量组显著上升(P0.01);随BDE-47浓度的变化,APE1蛋白表达量与细胞ROS水平存在一致性;p53、Bax、Caspase 8 m RNA表达量与BDE-47的浓度间存在剂量-效应关系。结果表明,BDE-47可诱导HEK293细胞凋亡及氧化应激,APE1可能是细胞ROS升高与细胞凋亡间重要的中介因子;BDE-47可以通过影响Caspase 8及线粒体途径中p53及Bax的表达诱导细胞凋亡。

The Toxicological Effects and Mechanisms of BDE-47 on HEK293 Cells

Three BDE-47 concentration groups (low: 10-6 mol·L^-1, medium: 10-5 mol·L^-1, high: 10-4 mol·L^-1) and one control group were chosen to investigate the toxic effects of BDE-47 on HEK293 cells, including cell apoptosis ratio and ROS level. Furthermore, the abundance of several proteins (APE1 and p53) and expression level of p53, Bax, Caspase 8 were also detected at molecular level. It was found that cell apoptosis was significantly increased in the medium and high concentration groups (P< 0.05) compared with the control. ROS level also increased significantly in the medium concentration group (P< 0.01). With the increase of BDE-47 concentrations, the variation trend of APE1 abundance was coincident with that of ROS level. Moreover, the mRNA expression level of apoptosis-related genes (p53, Bax and Caspase 8) was up-regulated with the increase of BDE-47 concentrations. These results showed that BDE-47 could cause several toxic effects on HEK293 cells, including induction of cell apoptosis and oxidative stress. APE1 was perhaps an important mediator of cell apoptosis and oxidative stress. BDE-47 could induce cell apoptosis by affecting the expression of Caspase 8 and p53, Bax through the mitochondria signal pathway.