著者

Natsumi Seki Masahiro Akiyama Hiroto Yamakawa Koji Hase Yoshito Kumagai Yun-Gi Kim

出版者

The Japanese Society of Toxicology

雑誌

The Journal of Toxicological Sciences (ISSN:03881350)

巻号頁・発行日

vol.46, no.2, pp.91-97, 2021 (Released:2021-02-02)

参考文献数

29

被引用文献数

5 12

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Methylmercury (MeHg), an environmental electrophile, binds covalently to the cysteine residues of proteins in organs, altering protein function and causing cytotoxicity. MeHg has also been shown to alter the composition of gut microbes. The gut microbiota is a complex community, the disturbance of which has been linked to the development of certain diseases. However, the relationship between MeHg and gut bacteria remains poorly understood. In this study, we showed that MeHg binds covalently to gut bacterial proteins via cysteine residues. We examined the effects of MeHg on the growth of selected Lactobacillus species, namely, L. reuteri, L. gasseri, L. casei, and L. acidophilus, that are frequently either positively or negatively correlated with human diseases. The results revealed that MeHg inhibits the growth of Lactobacillus to varying degrees depending on the species. Furthermore, the growth of L. reuteri, which was inhibited by MeHg exposure, was restored by Na2S2 treatment. By comparing mice with and without gut microbiota colonization, we found that gut bacteria contribute to the production of reactive sulfur species such as hydrogen sulfide and hydrogen persulfide in the gut. We also discovered that the removal of gut bacteria accelerated accumulation of mercury in the cerebellum, liver, and lungs of mice subsequent to MeHg exposure. These results accordingly indicate that MeHg is captured and inactivated by the hydrogen sulfide and hydrogen persulfide produced by intestinal microbes, thereby providing evidence for the role played by gut microbiota in reducing MeHg toxicity.

著者

Musubu Takahashi Ayaka Kubota Tomoya Fujie Yasuhiro Shinkai Yoshito Kumagai Tsuyoshi Nakano Takato Hara Chika Yamamoto Toshiyuki Kaji

出版者

The Pharmaceutical Society of Japan

雑誌

BPB Reports (ISSN:2434432X)

巻号頁・発行日

vol.4, no.6, pp.175-181, 2021 (Released:2021-11-12)

参考文献数

27

被引用文献数

2

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Fibroblast growth factor-2 (FGF-2) regulates several vascular endothelial cell functions, including proliferation. It has been suggested that the regulation may be modulated by reactive sulfur species (RSS), which are hydrogen sulfide and biomolecules containing persulfide/polysulfide groups. Since RSS promote vascular endothelial cell proliferation, we hypothesized that FGF-2 regulates the levels of RSS-producing enzymes in the cells. Bovine aortic endothelial cells were cultured and treated with FGF-2, and intracellular RSS levels were determined. The expression of RSS-producing enzymes, cystathionine γ-lyase (CSE), cystathionine β-synthase, 3-mercaptopyruvate sulfurtransferase, and cysteinyl-tRNA synthetase 2, was evaluated, and the intracellular signaling pathway that mediates FGF-2 regulation of RSS accumulation was investigated. We revealed that FGF-2 upregulates the expression of RSS by selectively inducing CSE via the ERK1/2 signaling pathway in vascular endothelial cells. The effect of FGF-2 on the function of vascular endothelial cells may be modulated by intracellular RSS, especially higher-molecular-mass RSS such as protein persulfide, the levels of which are increased by the growth factor.