Trimethyltin induces apoptosis and necroptosis of mouse liver by oxidative stress through YAP phosphorylation

• Published in: Ecotoxicology and environmental safety Vol. 248; p. 114327
• Main Authors: Wang, Yuqi, Liu, Xiaojing, Jing, Hongyuan, Ren, Haoran, Xu, Shiwen, Guo, Mengyao
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 15.12.2022; Elsevier
• Subjects: Apoptosis; Liver; Necroptosis; Oxidative stress; P-YAP; Trimethyltin; Oxidative stress; Necroptosis; Trimethyltin; Liver; P-YAP; Apoptosis
• ISSN: 0147-6513; 1090-2414
• DOI: 10.1016/j.ecoenv.2022.114327

Trimethyltin (TMT) is widely used as a major component of plastic stabilizers in agriculture and industry, and can accumulate in large quantities in the liver. To investigate the relationship between liver tissue damage induced by TMT exposure and YAP phosphorylation in mice, we gave the mice drinking water containing 0.01 mg/mL TMT for 14 days to establish an in vivo experimental model, and continuously treated AML12 cells with 20 μM TMT for 24 h to establish an in vitro experimental model. Transcriptomics revealed that TMT exposure altered 62,466 apparently diversely expressed genes, including 1197 upregulated and 899 downregulated genes, and that enrichment of the Hippo pathway occurred. Moreover, western blotting (WB) and quantitative real-time PCR (qRTPCR) results showed that TMT exposure triggered an increase in the expression of P-YAP, apoptosis and necroptosis-interrelated genes, and a decrease in Bcl-2 expression in mouse livers tissues and AML12 cells. The expression of P-YAP was significantly suppressed in the TRULI-treated TMT-exposed AML12 cells, while oxidative stress levels and damage were also significantly attenuated. In conclusion, TMT triggers YAP phosphorylation to induce oxidative stress inducing apoptosis and necroptosis in mouse livers tissues. Our results confirm the liver toxic effect and specific mechanism of TMT. [Display omitted] •TMT exposure induced liver injury in mice.•TMT poisoning causes phosphorylation of YAP leading to oxidative stress.•Oxidative stress induced necroptosis and apoptosis in mouse liver and ALM12 cells.