微塑料联合MEHP抑制SIRT3/SOD2诱导肝细胞线粒体损伤和氧化应激
Microplastics Combined with MEHP Induced Mitochondrial Damage and Oxidative Stress via Inhibiting SIRT3/SOD2 in Hepatocytes
王晓曼 1石东星 2韩艳阳 1董亚静 1韩浩2
作者信息
- 1. 山西医科大学公共卫生学院,太原 030001
- 2. 山西医科大学公共卫生学院,太原 030001;山西医科大学营养与食品科学研究所,太原 030001;山西医科大学煤炭环境致病与防治教育部重点实验室,太原 030001;山西医科大学黄河流域生态公共卫生安全研究中心,太原 030001
- 折叠
摘要
微塑料(microplastics,MPs)常与多种塑料相关产品共同暴露损害人体健康.邻苯二甲酸二(2-乙基己基)酯(di-2-ethylhexyl phthalate,DEHP)是常见的塑化剂,其主要代谢物为邻苯二甲酸单(2-乙基己基)酯(mono-2-ethylhexyl phthalate,MEHP).MPs与MEHP进入机体后均在肝脏蓄积,因此研究MPs与MEHP的联合暴露对肝脏的毒性效应及潜在机制具有重要意义.本研究采用聚苯乙烯微塑料(polystyrene microplastics,PS-MPs)和MEHP单独及二者联合处理HepG2细胞,检测细胞活力、活性氧水平、线粒体膜电位、COXI、COXⅢ、SIRT3和SOD2的蛋白表达水平.结果表明,PS-MPs和MEHP单独暴露均引起活性氧生成增加、线粒体膜电位降低.PS-MPs单独暴露也导致COXI与COXⅢ蛋白表达水平降低.两者联合暴露时上述有害作用更为显著,为协同效应.进一步的分子机制研究表明,PS-MPs下调了 SIRT3和SOD2蛋白表达,MEHP下调了 SIRT3蛋白表达,而PS-MPs和MEHP联合暴露对SIRT3和SOD2的蛋白表达的影响表现为协同效应.综上所述,PS-MPs和MEHP联合暴露导致HepG2细胞氧化应激和线粒体损伤,其分子机制与抑制SIRT3/SOD2信号通路有关.
Abstract
Microplastics(MPs)are usually co-exposed with a variety of plastic-related products.This co-exposed is harmful to human health.Mono-2-ethylhexyl phthalate(MEHP)is a primary metabolite of di-2-ethylhexyl phthalate(DEHP),a common plasticizer.Once entering into the body,MPs and MEHP accumulate in the liver.Therefore,it is important to study the toxic effects of the co-exposed of MPs and MEHP on the liver and explore the potential mechanisms.In this study,HepG2 cells were treated with polystyrene microplastics(PS-MPs),MEHP,or PS-MPs combined with MEHP.The cell viability,reactive oxygen species(ROS),mitochondrial membrane potential(MMP),and protein expression of COXⅠ,COXⅢ,SIRT3 and SOD2 were measured.The results showed that PS-MPs or MEHP exposure increased ROS generation and decreased MMP.PS-MPs exposure alone reduced protein expression of COXⅠ and COXⅢ.These harmful effects were more pronounced when combined exposure,indicated a synergistic effect.Further molecular mechanism study exhibited that PS-MPs treatment down-regulated the protein expression of SIRT3 and SOD2.MEHP treatment down-regulated the protein expression of SIRT3.The combined exposure of PS-MPs and MEHP synergistically down-regulated the protein expression of SIRT3 and SOD2.In summary,the combined exposure of PS-MPs and MEHP resulted in oxidative stress and mitochondrial damage in HepG2 cells,and the underlying molecular mechanism is related to the inhibition of the SIRT3/SOD2 signaling pathway.
关键词
微塑料/MEHP/HepG2细胞/联合暴露/氧化应激/线粒体损伤/SIRT3Key words
microplastics/MEHP/HepG2 cells/combined exposure/oxidative stress/mitochondrial damage/SIRT3引用本文复制引用
基金项目
山西省应用基础研究计划基金项目(202103021223223)
山西省应用基础研究计划基金项目(202303021211124)
出版年
2024
NETL
NSTL
万方数据