内质网
自噬
细胞生物学
化学
程序性细胞死亡
未折叠蛋白反应
细胞周期检查点
细胞周期
细胞凋亡
生物
生物化学
作者
Pengchen Chen,Yali Song,Li Tang,Wenbin Zhong,Jingjing Zhang,Min Cao,Junhui Chen,Guangqing Cheng,Huiying Li,Tianyun Fan,Hang Fai Kwok,Jigang Wang,Chuanbin Yang,Wei Xiao
标识
DOI:10.1016/j.jhazmat.2023.130785
摘要
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.
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