Interaction of 9,10-phenanthraquinone with dithiol causes oxidative modification of Cu,Zn-superoxide dismutase (SOD) through redox cycling

• Koizumi Rie

  Master’s Program in Environmental Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba

• Taguchi Keiko

  Doctoral Program in Biomedical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba

• Hisamori Miwa

  Master’s Program in Environmental Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba

• Kumagai Yoshito

  Doctoral Program in Biomedical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba

抄録

9,10-Phenanthraquinone (9,10-PQ) is abundant in diesel exhaust particles (DEP) and causes oxidative protein modification in cells. We previously reported that redox cycling of 9,10-PQ with dithiols leads to the generation of an excess of superoxide (O₂^•−). Cu,Zn-superoxide dismutase (Cu,Zn-SOD), which dismutates O₂^•− to hydrogen peroxide (H₂O₂), is sensitive to its own product, H₂O₂. In this study, incubating 9,10-PQ with dithiols, but not monothiols, for 24 hr, resulted in the conversion of native Cu,Zn-SOD to its charge isomers, some of which did not show enzyme activity. Exposing Cu,Zn-SOD to 9,10-PQ in the presence of dihydrolipoic acid (DHLA), a model for low molecular weight endogenous dithiols, caused a concentration-dependent decrease in the enzyme activity. Under these conditions, copper release from the active site and Cu,Zn-SOD oxidation were detected, the evidence for which was carbonyl formation. Experiments using agents that scavenge reactive oxygen species (ROS) indicated that the hydroxyl radical (•OH) derived from H₂O₂ plays a critical role in the fragmentation of the enzyme. The findings presented suggest that Cu,Zn-SOD readily undergoes oxidative modification associated with activity loss, caused by ROS generated by the redox cycling of 9,10-PQ with endogenous dithiols such as DHLA and, presumably, proximal protein thiols.

収録刊行物

• Ｔｈｅ　Ｊｏｕｒｎａｌ　ｏｆ　Ｔｏｘｉｃｏｌｏｇｉｃａｌ　Ｓｃｉｅｎｃｅｓ

  Ｔｈｅ　Ｊｏｕｒｎａｌ　ｏｆ　Ｔｏｘｉｃｏｌｏｇｉｃａｌ　Ｓｃｉｅｎｃｅｓ 38 (3), 317-324, 2013

  一般社団法人　日本毒性学会

キーワード

• Cu,Zn-superoxide dismutase
• Quinone
• Oxidative modification
• Dihydrolipoic acid
• Charge isomer

詳細情報

• CRID: 1390001204906148224
• NII論文ID: 10031158897
• NII書誌ID: AN00002808
• DOI: 10.2131/jts.38.317
• COI: 1:CAS:528:DC%2BC3sXhtVKhs7fN
• ISSN: 18803989
• ISSN: 03881350
• NDL書誌ID: 024783913
• PubMed: 23665930
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I024783913
• Web Site: https://www.jstage.jst.go.jp/article/jts/38/3/38_317/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2014081394
• 本文言語コード: en
• データソース種別:
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  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
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