3-MCPD棕榈酸酯通过JNK1/p53通路诱导NRK-52E细胞凋亡
3-Chloro-1,2-Propanediol Palmitate Ester Induced NRK-52E Cell Apoptosis through Activating JNK1/p53 Pathway

氯-1,2-丙二醇(3-MCPD)脂肪酸酯是一类在食品加工过程中产生的有害物质,关于其毒性机制尚不明确。本文以大鼠肾细胞NRK-52E为模型,采用RNA干扰技术,研究3-MCPD-1-棕榈酸单酯(C16:0-ME)诱导肾细胞凋亡过程中JNK及p53的靶向调控作用,以及JNK1、JNK2和JNK3亚型在肾损伤过程中发挥的作用。结果表明,采用浓度为300 μmol/L的C16:0-ME处理细胞24 h,JNK及p53磷酸化水平均显著提高,细胞凋亡相关蛋白bax及cleaved caspase-3表达量显著上调,bcl-2表达被明显抑制。当采用shRNA沉默p53蛋白表达后,采用浓度为300 μmol/L的C16:0-ME处理细胞24 h,bax及cleaved caspase-3的表达均被抑制。在JNK 3个亚型中,只有JNK1 shRNA处理组能显著减轻C16:0-ME引起的肾细胞凋亡,p-c-Jun、bax、cleaved caspase-3、p53及p-p53的表达明显被抑制。研究结果表明,C16:0-ME通过JNK1/p53通路诱导肾细胞凋亡。
chloro-1,2-propanediol fatty esters are common food contaminants formed during food processing.However,the toxic mechanisms remain unclear.This study was designed to investigate the roles of JNK and p53 in NRK-52E cell apoptosis induced by 3-chloro-1,2-propanediol palmitate ester (C16:0-ME) using short hairpin RNA.Moreover,the roles of JNK1,JNK2 and JNK3 subtypes were also examined.The results suggested that the phosphorylation of JNK and p53 was significantly increased in NRK-52E cells treated with C16:0-ME at 300 μmol/L for 24 h.The bax and cleaved caspase-3 protein levels were both significantly up-regulated,while the expression of bcl-2 was significantly inhibited by C16:0-ME.Additionally,p53 knockdown attenuated the apoptosis and the apoptosis-related protein bax and cleaved caspase-3 expression was inhibited by C16:0-ME in cells treated with p53 shRNA.Among the three JNK subtypes,only JNK1 shRNA blocked the kidney cell apoptosis and p-c-Jun,bax,cleaved caspase-3,p53 and p-p53 expression induced by C16:0-ME.The results indicated that C16:0-ME induced kidney cell apoptosis via activating JNK1/p53 pathway.