S-Mercuration of ubiquitin carboxyl-terminal hydrolase L1 through Cys152 by methylmercury causes inhibition of its catalytic activity and reduction of monoubiquitin levels in SH-SY5Y cells

• Toyama Takashi

  Faculty of Medicine, University of Tsukuba Present address: Laboratory of Molecular and Biochemical Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University

• Abiko Yumi

  Faculty of Medicine, University of Tsukuba

• Katayama Yuko

  Graduate School of Life and Environmental Sciences, University of Tsukuba

• Kaji Toshiyuki

  Faculty of Pharmaceutical Sciences, Tokyo University of Science

• Kumagai Yoshito

  Faculty of Medicine, University of Tsukuba Graduate School of Life and Environmental Sciences, University of Tsukuba

書誌事項

タイトル別名

• <i>S</i>-Mercuration of ubiquitin carboxyl-terminal hydrolase L1 through Cys152 by methylmercury causes inhibition of its catalytic activity and reduction of monoubiquitin levels in SH-SY5Y cells

抄録

Methylmercury (MeHg) is an environmental electrophile that covalently modifies cellular proteins. In this study, we identified proteins that undergo S-mercuration by MeHg. By combining two-dimensional SDS-PAGE, atomic absorption spectrometry and ultra performance liquid chromatography mass spectrometry (UPLC/MS/MS), we revealed that ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) is a target for S-mercuration in human neuroblastoma SH-SY5Y cells exposed to MeHg (1 µM, 9 hr). The modification site of UCH-L1 by MeHg was Cys152, as determined by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. MeHg was shown to inhibit the catalytic activity of recombinant human UCH-L1 in a concentration-dependent manner. Knockdown of UCH-L1 indicated that this enzyme plays a critical role in regulating mono-ubiquitin (monoUb) levels in SH-SY5Y cells and exposure of SH-SY5Y cells to MeHg caused a reduction in the level of monoUb in these cells. These observations suggest that UCH-L1 readily undergoes S-mercuration by MeHg through Cys152 and this covalent modification inhibits UCH-L1, leading to the potential disruption of the maintenance of cellular monoUb levels.

収録刊行物

• Ｔｈｅ　Ｊｏｕｒｎａｌ　ｏｆ　Ｔｏｘｉｃｏｌｏｇｉｃａｌ　Ｓｃｉｅｎｃｅｓ

  Ｔｈｅ　Ｊｏｕｒｎａｌ　ｏｆ　Ｔｏｘｉｃｏｌｏｇｉｃａｌ　Ｓｃｉｅｎｃｅｓ 40 (6), 887-893, 2015

  一般社団法人　日本毒性学会

キーワード

• Electrophile
• Methylmercury
• <i>S</i>-Mercuration
• UCH-L1

詳細情報

• CRID: 1390282679880095104
• NII論文ID: 130005108872
• NII書誌ID: AN00002808
• DOI: 10.2131/jts.40.887
• ISSN: 18803989
• ISSN: 03881350
• HANDLE: 2241/00154161
• NDL書誌ID: 026971393
• PubMed: 26558469
• Web Site: https://tsukuba.repo.nii.ac.jp/records/48688
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I026971393
• Web Site: https://www.jstage.jst.go.jp/article/jts/40/6/40_887/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2016248658
• 本文言語コード: en
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