Tributyltin chloride (TBTCL) induces cell injury via dysregulation of endoplasmic reticulum stress and autophagy in Leydig cells

Chen, Pengchen1; Song, Yali; Tang, Li; Zhong, Wenbin1; Zhang, JingJing2,3; Cao, Min; Chen, Junhui2,3; Cheng, Guangqing6,7; Li, Huiying1; Fan, Tianyun1; Kwok, Hang Fai5; Wang, Jigang1,2,3,6,7; Yang, Chuanbin1,2,3; Xiao, Wei1,4

2023-04-15

10.1016/j.jhazmat.2023.130785

JOURNAL OF HAZARDOUS MATERIALS   Impact Factor & Quartile

0304-3894

1873-3336

Tributyltin chloride (TBTCL), a commonly used antiseptic substance, is commonly found in the environment. Human exposure to TBTCL through the consumption of contaminated seafood, fish, or drinking water has aroused concern. It is well-characterized that TBTCL has multiple detrimental effects on the male reproductive system. However, the potential cellular mechanisms are not fully elucidated. Here, we characterized molecular mechanisms of TBTCL-induced cell injury in Leydig cells, a critical supporter for spermatogenesis. We showed that TBTCL induces apoptosis and cell cycle arrest in TM3 mouse Leydig cells. RNA sequencing analyses revealed that endoplasmic reticulum (ER) stress and autophagy were potentially involved in TBTCL-induced cytotoxicity. We further showed that TBTCL causes ER stress and inhibited autophagy flux. Notably, the inhibition of ER stress attenuates not only TBTCL-induces autophagy flux inhibition but also apoptosis and cell cycle arrest. Meanwhile, the activation of autophagy alleviates, and inhibition of autophagy exaggerates TBTCL-induced apoptosis and cell cycle arrest flux. These results suggest that TBTCL-induced ER stress and autophagy flux inhibition contributed to apoptosis and cell cycle arrest in Leydig cells, providing novel understanding into the mechanisms of TBTCL-induced testis toxicity.

Tributyltin chloride Leydig cell Endoplasmic reticulum stress Autophagy

SCI

English

Corresponding

China Postdoctoral Science Foundation[K122292027] ; National Key Research and Development Program of China["2020YFA0908000","2022YFC2303600"] ; Innovation Team and Talents Cultivation Program of National Admin- istration of Traditional Chinese Medicine[ZYYCXTD-C-202002] ; National Natural Science Foundation of China["82141001","82274182","82074098","82173914"] ; Science and Technology Foundation of Shenzhen["JCYJ20210324115800001","JCYJ20220818102613029"] ; Shenzhen Governmental Sustainable Development Fund[KCXFZ20201221173 612034] ; Shenzhen key Laboratory of Kidney Diseases[ZDSYS201504301616234] ; Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties[SZGSP001] ; Guangdong-Dongguan Joint Fund Regional Cultivation Project[2021B1515140033] ; Dongguan Science and Technology of Social Development Program[20221800905732]

Engineering ; Environmental Sciences & Ecology

Engineering, Environmental ; Environmental Sciences

WOS:000942642600001

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1.Postdoctoral Innovat Practice Base Southern Med Un, Dongguan Maternal & Child Hlth Care Hosp, Dongguan 523125, Guangdong, Peoples R China
2.Southern Univ Sci & Technol, Jinan Univ, Shenzhen Peoples Hosp, Affiliated Hosp 1,Clin Med Coll 2,Dept Nephrol,She, Shenzhen 518020, Peoples R China
3.Southern Univ Sci & Technol, Jinan Univ, Shenzhen Peoples Hosp, Affiliated Hosp 1,Clin Med Coll 2,Shenzhen Clin Re, Shenzhen 518020, Peoples R China
4.Guangdong Pharmaceut Univ, Key Lab Glucolipid Metab Disorder, Minist Educ, Guangzhou 510006, Peoples R China
5.Univ Macau, Fac Hlth Sci, Dept Biomed Sci, Ave Univ, Taipa, Macao, Peoples R China
6.China Acad Chinese Med Sci, Artemisinin Res Ctr, Beijing 100700, Peoples R China
7.China Acad Chinese Med Sci, Inst Chinese Mat Med, Beijing 100700, Peoples R China

Chen, Pengchen,Song, Yali,Tang, Li,et al. Tributyltin chloride (TBTCL) induces cell injury via dysregulation of endoplasmic reticulum stress and autophagy in Leydig cells[J]. JOURNAL OF HAZARDOUS MATERIALS,2023,448.

Chen, Pengchen.,Song, Yali.,Tang, Li.,Zhong, Wenbin.,Zhang, JingJing.,...&Xiao, Wei.(2023).Tributyltin chloride (TBTCL) induces cell injury via dysregulation of endoplasmic reticulum stress and autophagy in Leydig cells.JOURNAL OF HAZARDOUS MATERIALS,448.

Chen, Pengchen,et al."Tributyltin chloride (TBTCL) induces cell injury via dysregulation of endoplasmic reticulum stress and autophagy in Leydig cells".JOURNAL OF HAZARDOUS MATERIALS 448(2023).