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.

中文翻译：

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METTL7B酶生物活化机制介导的甲硫醇在16HBE细胞中的强效坏死作用。

甲硫醇是一种广泛存在的恶臭污染物，对人类健康有影响。然而，甲硫醇在体外的细胞毒性机制及其代谢转化（生物活化或解毒）尚未完全阐明。在此，研究了细胞培养过程中甲硫醇的代谢物和甲硫醇在人支气管上皮 (16HBE) 细胞中的细胞毒性。结果表明，甲硫醇（10-50 μM）在16HBE细胞中主要被硫醇S-甲基转移酶催化部分转化为二甲硫醚，然后诱导强细胞毒性和细胞膜通透性。此外，甲硫醇可诱导高达 50 μM 的细胞内活性氧 (ROS) 并进一步激活肿瘤坏死因子 (TNF) 信号通路，最终导致线粒体膜电位（MMP）下降和细胞坏死。然而，甲基转移酶样蛋白 7B (METTL7B) 的基因沉默显着减轻了所有这些影响。这些结果表明，甲硫醇可能在人呼吸道细胞中诱导细胞坏死，主要由 S-甲基转移酶介导，干扰 TNF 和 ROS 的诱导。非目标代谢组学结果表明，甲硫醇有效影响 16HBE 细胞中内源性小分子代谢物的表达。这项工作在一定程度上展示了人体呼吸道细胞暴露于甲硫醇的可能转化路径和潜在损伤机制。甲基转移酶样蛋白 7B (METTL7B) 的基因沉默显着减轻了所有这些影响。这些结果表明，甲硫醇可能在人呼吸道细胞中诱导细胞坏死，主要由 S-甲基转移酶介导，干扰 TNF 和 ROS 的诱导。非目标代谢组学结果表明，甲硫醇有效影响 16HBE 细胞中内源性小分子代谢物的表达。这项工作在一定程度上展示了人体呼吸道细胞暴露于甲硫醇的可能转化路径和潜在损伤机制。甲基转移酶样蛋白 7B (METTL7B) 的基因沉默显着减轻了所有这些影响。这些结果表明，甲硫醇可能在人呼吸道细胞中诱导细胞坏死，主要由 S-甲基转移酶介导，干扰 TNF 和 ROS 的诱导。非目标代谢组学结果表明，甲硫醇有效影响 16HBE 细胞中内源性小分子代谢物的表达。这项工作在一定程度上展示了人体呼吸道细胞暴露于甲硫醇的可能转化路径和潜在损伤机制。非目标代谢组学结果表明，甲硫醇有效影响 16HBE 细胞中内源性小分子代谢物的表达。这项工作在一定程度上展示了人体呼吸道细胞暴露于甲硫醇的可能转化路径和潜在损伤机制。非目标代谢组学结果表明，甲硫醇有效影响 16HBE 细胞中内源性小分子代谢物的表达。这项工作在一定程度上展示了人体呼吸道细胞暴露于甲硫醇的可能转化路径和潜在损伤机制。