ヤマシタ　ナオヤ   山下　直哉    所属   東邦大学  薬学部 薬学科    職種   講師
論文種別	原著
言語種別
査読の有無	査読あり
表題	Methylmercury Induces Apoptosis in Mouse C17.2 Neural Stem Cells through the Induction of OSGIN1 Expression by NRF2
掲載誌名	正式名：International Journal of Molecular Sciences ISSNコード：1422-0067
出版社	MDPI AG
巻・号・頁	25(7),3886-3886頁
著者・共著者	Naoya Yamashita,Marino Uchiyama,Ryota Yamagata,Gi-Wook Hwang
担当区分	筆頭著者
発行年月	2024/03/30
概要	Methylmercury is a known environmental pollutant that exhibits severe neurotoxic effects. However, the mechanism by which methylmercury causes neurotoxicity remains unclear. To date, we have found that oxidative stress-induced growth inhibitor 1 (OSGIN1), which is induced by oxidative stress and DNA damage, is also induced by methylmercury. Therefore, in this study, we investigated the relationship between methylmercury toxicity and the induction of OSGIN1 expression using C17.2 cells, which are mouse brain neural stem cells. Methylmercury increased both OSGIN1 mRNA and protein levels in a time- and concentration-dependent manner. Moreover, these increases were almost entirely canceled out by pretreatment with actinomycin D, a transcription inhibitor. Furthermore, similar results were obtained from cells in which expression of the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) was suppressed, indicating that methylmercury induces OSGIN1 expression via NRF2. Methylmercury causes neuronal cell death by inducing apoptosis. Therefore, we next investigated the role of OSGIN1 in methylmercury-induced neuronal cell death using the activation of caspase-3, which is involved in apoptosis induction, as an indicator. As a result, the increase in cleaved caspase-3 (activated form) induced by methylmercury exposure was decreased by suppressing OSGIN1, and the overexpression of OSGIN1 further promoted the increase in cleaved caspase-3 caused by methylmercury. These results suggest, for the first time, that OSGIN1 is a novel factor involved in methylmercury toxicity, and methylmercury induces apoptosis in C17.2 cells through the induction of OSGIN1 expression by NRF2.
DOI	10.3390/ijms25073886
PermalinkURL	https://www.mdpi.com/1422-0067/25/7/3886/pdf