Trimethyltin induces apoptosis and necroptosis of mouse liver by oxidative stress through YAP phosphorylation
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 drinki...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-12-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651322011678 |
| _version_ | 1811315930702020608 |
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| author | Yuqi Wang Xiaojing Liu Hongyuan Jing Haoran Ren Shiwen Xu Mengyao Guo |
| author_facet | Yuqi Wang Xiaojing Liu Hongyuan Jing Haoran Ren Shiwen Xu Mengyao Guo |
| author_sort | Yuqi Wang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T11:40:10Z |
| format | Article |
| id | doaj.art-e7dfa8af78eb4f3c8a9a79a4458e7c00 |
| institution | Directory Open Access Journal |
| issn | 0147-6513 |
| language | English |
| last_indexed | 2024-04-13T11:40:10Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj.art-e7dfa8af78eb4f3c8a9a79a4458e7c002022-12-22T02:48:20ZengElsevierEcotoxicology and Environmental Safety0147-65132022-12-01248114327Trimethyltin induces apoptosis and necroptosis of mouse liver by oxidative stress through YAP phosphorylationYuqi Wang0Xiaojing Liu1Hongyuan Jing2Haoran Ren3Shiwen Xu4Mengyao Guo5College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China; Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China; Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China; Corresponding author at: College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China.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.http://www.sciencedirect.com/science/article/pii/S0147651322011678TrimethyltinLiverP-YAPOxidative stressNecroptosisApoptosis |
| spellingShingle | Yuqi Wang Xiaojing Liu Hongyuan Jing Haoran Ren Shiwen Xu Mengyao Guo Trimethyltin induces apoptosis and necroptosis of mouse liver by oxidative stress through YAP phosphorylation Ecotoxicology and Environmental Safety Trimethyltin Liver P-YAP Oxidative stress Necroptosis Apoptosis |
| title | Trimethyltin induces apoptosis and necroptosis of mouse liver by oxidative stress through YAP phosphorylation |
| title_full | Trimethyltin induces apoptosis and necroptosis of mouse liver by oxidative stress through YAP phosphorylation |
| title_fullStr | Trimethyltin induces apoptosis and necroptosis of mouse liver by oxidative stress through YAP phosphorylation |
| title_full_unstemmed | Trimethyltin induces apoptosis and necroptosis of mouse liver by oxidative stress through YAP phosphorylation |
| title_short | Trimethyltin induces apoptosis and necroptosis of mouse liver by oxidative stress through YAP phosphorylation |
| title_sort | trimethyltin induces apoptosis and necroptosis of mouse liver by oxidative stress through yap phosphorylation |
| topic | Trimethyltin Liver P-YAP Oxidative stress Necroptosis Apoptosis |
| url | http://www.sciencedirect.com/science/article/pii/S0147651322011678 |
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