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

作　　者：薛金丽[1] 刘曼 黄国任 孙向军[1] 俞良莉 

机构地区：[1]上海交通大学农业与生物学院,上海200240 [2]马里兰大学营养与食品科学系,马里兰20742

出　　处：《上海交通大学学报（农业科学版）》2017年第6期14-19,共6页Journal of Shanghai Jiaotong University(Agricultural Science)

基　　金：国家高技术研究发展计划(2013AA102202)

摘　　要：3-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300μmol/L的C_(16:0)-ME处理细胞24h,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300μmol/L的C_(16:0)-ME处理细胞24h,bax及cleaved caspase-3的表达均被抑制。在JNK 3个亚型中,只有JNK1shRNA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。3-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 （C16：0-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^G,0-ME at 300 ~mol/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 C16,0-ME. Additionally,p53 knockdown attenuated the apoptosis and the apoptosis-related protein bax and cleaved caspase-3 expression was inhibited by C16,0-ME in cells treated with p53 shRNA. Among the three JNK subtypes, only J NK1 shRNA blocked the kidney cell apoptosis and p-c-Jun, bax, cleaved caspase-3, p53 andp-p53 expression induced by C16,o-ME. The results indicated that C16,0-ME induced kidney cell apoptosis via activating JNK1/p53 pathway.

关 键 词：3-MCPD-1-棕榈酸单酯 肾损伤 细胞凋亡 JNK p53 

分 类 号：R692[医药卫生—泌尿科学]