Lipid metabolic disturbance induced by triphenyl phosphate and hydroxy metabolite in HepG2 cells

被引:13
作者
An, Jing [1 ]
Jiang, Jingjing [1 ]
Tang, Waner [1 ]
Zhong, Yufang [1 ]
Ren, Guofa [1 ]
Shang, Yu [1 ]
Yu, Zhiqiang [2 ,3 ,4 ]
机构
[1] Shanghai Univ, Inst Environm Pollut & Hlth, Sch Environm & Chem Engn, Shanghai 200444, Peoples R China
[2] Chinese Acad Sci, Guangzhou Inst Geochem, State Key Lab Organ Geochem, Guangdong Prov Key Lab Environm Protect & Resource, Guangzhou 510640, Peoples R China
[3] CAS Ctr Excellence Deep Earth Sci, Guangzhou 510640, Peoples R China
[4] Chinese Acad Sci, Guangzhou Inst Geochem, CAS Ctr Excellence Deep Earth Sci, Guangzhou 510640, Peoples R China
基金
中国国家自然科学基金;
关键词
Triphenyl phosphate (TPHP); OH-TPHP; DPHP; Lipid metabolism; PPARs signal pathway; Endoplasmic reticulum stress; ORGANOPHOSPHORUS FLAME RETARDANTS; EXPOSURE; EXPRESSION; LIVER; ACCUMULATION; PLASTICIZERS; DUST; CYTOTOXICITY; CHOLESTEROL; ASSOCIATION;
D O I
10.1016/j.ecoenv.2023.115160
中图分类号
X [环境科学、安全科学];
学科分类号
08 ; 0830 ;
摘要
Triphenyl phosphate (TPHP) has been widely used as flame retardants and been detected with increasing frequency in environment. TPHP can transform into mono-hydroxylated phosphate (OH-TPHP) and diester diphenyl phosphate (DPHP) through biotransformation. So far, information on the cytotoxicity and molecular regulatory mechanisms of TPHP metabolites are still limit. This study investigated the adverse effects of TPHP, OH-TPHP, and DPHP in HepG2 cells in terms of cell proliferation, lactate dehydrogenase release, reactive oxygen species generation, and mitochondrial membrane potential. The transcriptomic changes were measured using RNA sequencing, and bioinformatics characteristics including biological functions, signal pathways and proteinprotein interaction were analyzed to explore the potential molecular mechanisms. Results displayed that the order of cytotoxicity was OH-TPHP> TPHP> DPHP. The prioritized biological functions changes induced by TPHP and OH-TPHP were correlated with lipid metabolism. Significant lipid accumulation was observed as confirmed by increased total cholesterol and triglycerides contents, and enhanced oil red O staining. Enrichment of PPAR & alpha;/& gamma; and down-stream genes suggested the participation of PPARs signal pathway in lipid metabolism disorder. In addition, TPHP and OH-TPHP induced endoplasmic reticulum stress (ERS), which was further confirmed by the ERS inhibitor experiment. In general, TPHP and OH-TPHP had obvious cytotoxic effects in HepG2 cells. PPARs signal pathway and endoplasmic reticulum stress may be involved in the lipid metabolism disorder induced by TPHP and OH-TPHP.
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页数:10
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