Triphenyl phosphate (TPP) promotes hepatocyte toxicity via induction of endoplasmic reticulum stress and inhibition of autophagy flux

Li, Miaoran1,2,3; Liu, Gang1; Yuan, Li-Xia4; Yang, Jing2,3; Liu, Jing2,3; Li, Zhijie2,3; Yang, Chuanbin2,3; Wang, Jigang2,3,4,5

2022-09-20

10.1016/j.scitotenv.2022.156461

SCIENCE OF THE TOTAL ENVIRONMENT   Impact Factor & Quartile

0048-9697

1879-1026

Triphenyl phosphate (TPP), a commonly used organophosphate flame retardant, is frequently found in environmental and biota samples, indicating widespread human exposure. Recent studies have shown that TPP causes hepatotoxicity, but the underlying cellular mechanisms are not fully elucidated. Here, by using normal hepatocyte AML12 cells as a model, we showed that TPP induced apoptotic cell death. RNA sequencing analyses revealed that differentially expressed genes induced by TPP were related to endoplasmic reticulum (ER) stress and autophagy. Immunostaining and western blot results further confirmed that TPP activated ER stress. Interestingly, though TPP increased LC3-II, a canonical marker for autophagy, TPP inhibited autophagy flux rather than induced autophagy. Interestingly, TPPinduced ER stress facilitated autophagy flux inhibition and apoptosis. Furthermore, inhibition of autophagy aggravated, and activation of autophagy attenuated apoptosis induced by TPP. Collectively, these results uncovered that ER stress and autophagy flux inhibition were responsible for TPP-induced apoptosis in mouse hepatocytes. Thus, our foundlings provided novel insight into the potential mechanisms of TPP-induced hepatocyte toxicity.

Triphenyl phosphate Hepatoxicity ER stress Autophagy Apoptosis

SCI

English

Corresponding

Shenzhen Science and Technology Innovation Commission["JCYJ20210324115800001","JCYJ20210324114014039"] ; National Key Research and Development Program of China[2020YFA0908000] ; Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine[ZYYCXTD-C-20200 2]

Environmental Sciences & Ecology

Environmental Sciences

WOS:000816884800010

ELSEVIER

ENVIRONMENT/ECOLOGY

Web of Science

1.Southern Med Univ, Nanfang Hosp, Dept Rehabil Med, Guangzhou 510515, Peoples R China
2.Jinan Univ, Clin Med Coll 2, Shenzhen Peoples Hosp, Dept Geriatr Med, Shenzhen 518020, Peoples R China
3.Southern Univ Sci & Technol, Affiliated Hosp 1, Shenzhen 518020, Peoples R China
4.Southern Med Univ, Guangdong Prov Key Lab Chinese Med Pharmaceut, Sch Tradit Chinese Med, Guangzhou 510515, Peoples R China
5.Chinese Acad Chinese Med Sci, Inst Chinese Mat Med, Artemisinin Res Ctr, Beijing 100700, Peoples R China

Li, Miaoran,Liu, Gang,Yuan, Li-Xia,et al. Triphenyl phosphate (TPP) promotes hepatocyte toxicity via induction of endoplasmic reticulum stress and inhibition of autophagy flux[J]. SCIENCE OF THE TOTAL ENVIRONMENT,2022,840.

Li, Miaoran.,Liu, Gang.,Yuan, Li-Xia.,Yang, Jing.,Liu, Jing.,...&Wang, Jigang.(2022).Triphenyl phosphate (TPP) promotes hepatocyte toxicity via induction of endoplasmic reticulum stress and inhibition of autophagy flux.SCIENCE OF THE TOTAL ENVIRONMENT,840.

Li, Miaoran,et al."Triphenyl phosphate (TPP) promotes hepatocyte toxicity via induction of endoplasmic reticulum stress and inhibition of autophagy flux".SCIENCE OF THE TOTAL ENVIRONMENT 840(2022).