Potent necrosis effect of methanethiol mediated by METTL7B enzyme bioactivation mechanism in 16HBE cell.

Jinting Lei, Guiying Li, Hang Yu, Taicheng An

Ecotoxicology and environmental safety 2022 May 01

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Methanethiol is a widely existing malodorous pollutant with health effects on the human population. However, the cytotoxicity mechanism of methanethiol in vitro and its metabolic transformation (bioactivation or detoxification) have not been fully elucidated. Herein, the metabolites of methanethiol during cell culture and the cytotoxicity of methanethiol in human bronchial epithelial (16HBE) cells were investigated. Results indicate that methanethiol (10-50 μM) was partially converted into dimethyl sulfide, mainly catalyzed by thiol S-methyltransferase in the 16HBE cells, and then it induced potent cytotoxicity and cell membrane permeability. Moreover, methanethiol induced intracellular reactive oxygen species (ROS) up to 50 μM and further activated the tumor necrosis factor (TNF) signaling pathway, which eventually led to the decline in the mitochondrial membrane potential (MMP) and cell necrosis. However, all these effects were significantly alleviated with gene silencing of the methyltransferase-like protein 7B (METTL7B). These results indicate that methanethiol may induce cell necrosis in human respiratory tract cells mainly mediated by S-methyltransferase with interfering TNF and ROS induction. Non-target metabolomics results suggest that methanethiol potently affects expression of endogenous small molecule metabolites in 16HBE cells. To some extent, this work shows the possible conversion path and potential injury mechanism of human respiratory tract cells exposed to methanethiol. Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Jinting Lei, Guiying Li, Hang Yu, Taicheng An. Potent necrosis effect of methanethiol mediated by METTL7B enzyme bioactivation mechanism in 16HBE cell. Ecotoxicology and environmental safety. 2022 May 01;236:113486