1. A new insight into the mechanism of dichlorodiphenyltrichloroethane-induced hepatotoxicity based on GSDME-mediated pyroptosis.
- Author
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Tan, Jiaqi, Zhang, Chu, Bao, Ziyi, Zhao, Hanyang, Zhang, Li, and Xu, Hongxi
- Subjects
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APOPTOSIS , *LIVER cells , *CELL death , *PYROPTOSIS , *REACTIVE oxygen species - Abstract
There have been persistent concerns about the safety risks associated with DDT residues in the environment. Studies have shown that exposure to DDT or its metabolites can cause various liver diseases. However, the mechanisms of liver toxicity haven't been well studied. In our current investigation, we observed that DDT triggers pyroptosis in human liver cells (HL-7702), representing a novel form of programmed cell death. Our results delineated DDT (0–100 μM) induced pyroptosis in HL-7702 cells, which was confirmed through morphological changes, lactate dehydrogenase (LDH) release, gasdermin E (GSDME) cleavage and Annexin-V/PI staining. Knockdown of GSDME reduced cell death and transferred the mode of cell death from pyroptosis to apoptosis. Notably, DDT exposure markedly increased reactive oxygen species (ROS) production, concurrent with c-Jun N-terminal kinase (JNK) phosphorylation. Intervention with a ROS inhibitor or JNK inhibitor SP600125 restored cell viability and hindered GSDME-mediated pyroptosis. Our results firstly demonstrate that DDT suppresses HL-7702 cells growth by inducing pyroptosis mainly through the ROS/JNK/GSDME pathway. These findings not only contribute to an in-depth understanding of DDT toxicity but also open avenues for gaining valuable insights into potential mitigation strategies and therapeutic interventions. [Display omitted] • The study revealed the health risks linked to the impact of the pesticide DDT on human liver cells. • Our study has identified, for the first time, that DDT induced pyroptosis in HL-7702 cells. • The underlying mechanism behind DDT-induced pyroptosis was associated with ROS/JNK/GSDME pathway. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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