Induction of metallothionein isoforms by copper diethyldithiocarbamate in cultured vascular endothelial cells

• Fujie Tomoya

  Department of Environmental Health, Faculty of Pharmaceutical Sciences, Tokyo University of Science

• Segawa Yukino

  Department of Environmental Health, Faculty of Pharmaceutical Sciences, Tokyo University of Science

• Yoshida Eiko

  Department of Environmental Health, Faculty of Pharmaceutical Sciences, Tokyo University of Science

• Kimura Tomoki

  Depertment of Life Science, Faculty of Science and Engineering, Setsunan University

• Fujiwara Yasuyuki

  Department of Environmental Health, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences

• Yamamoto Chika

  Department of Environmental Health, Faculty of Pharmaceutical Sciences, Toho University

• Satoh Masahiko

  Laboratory of Pharmaceutical Health Sciences, School of Pharmacy, Aichi Gakuin University

• Naka Hiroshi

  Research Center for Materials Science, Nagoya University

• Kaji Toshiyuki

  Department of Environmental Health, Faculty of Pharmaceutical Sciences, Tokyo University of Science

抄録

Metallothionein (MT) plays a central role in cellular defense against heavy metals and oxidative stress. Since the induction of MT requires the activation of metal response element (MRE)-binding transcription factor-1 (MTF-1) by binding of zinc ions, inorganic zinc is regarded as a typical MT inducer. However, in a previous report, we showed that inorganic zinc could not induce MT in vascular endothelial cells. While it is suggested that endothelial MT presents mechanisms different from those of other cell types, these remain unclear. In this study, we investigated whether the induction of endothelial MT expression involves the Nrf2–ARE pathway using copper(II) bis(diethyldithiocarbamate), termed Cu10, using a culture system of bovine aortic endothelial cells. Cu10 induced MT-1/2 protein expression and increased the expression of mRNAs for MT-1A, MT-1E, and MT-2, MT isoforms expressed in the cells. Cu10 activated not only the MTF-1–MRE, but also the Nrf2–ARE pathway. MTF-1 knockdown resulted in the repression of Cu10-induced MT-1 and -2 expression. Cu10-induced MT-1 expression was down-regulated by Nrf2 knockdown. However, MT-2 expression was not affected by Nrf2 knockdown. These results suggest that the expression of endothelial MT is up-regulated by the Nrf2–ARE pathway as well as by the MTF-1–MRE pathway. Moreover, MT-1 regulation mechanisms differ from that of MT-2. Specifically, the present data support the hypothesis that MT-1 participates in the biological defense system, while MT-2 mainly regulates intracellular zinc metabolism.

収録刊行物

• Ｔｈｅ　Ｊｏｕｒｎａｌ　ｏｆ　Ｔｏｘｉｃｏｌｏｇｉｃａｌ　Ｓｃｉｅｎｃｅｓ

  Ｔｈｅ　Ｊｏｕｒｎａｌ　ｏｆ　Ｔｏｘｉｃｏｌｏｇｉｃａｌ　Ｓｃｉｅｎｃｅｓ 41 (2), 225-232, 2016

  一般社団法人　日本毒性学会

キーワード

• Copper complex
• Metallothionein
• Endothelial cell
• Bio-organometallics

詳細情報

• CRID: 1390001204905925888
• NII論文ID: 130005132663
• NII書誌ID: AN00002808
• DOI: 10.2131/jts.41.225
• ISSN: 18803989
• ISSN: 03881350
• NDL書誌ID: 027267880
• PubMed: 26961606
• Web Site: http://id.ndl.go.jp/bib/027267880
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I027267880
• Web Site: https://www.jstage.jst.go.jp/article/jts/41/2/41_225/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2016296487
• 本文言語コード: en
• データソース種別:
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