Interaction of 9,10-phenanthraquinone with dithiol causes oxidative modification of Cu,Zn-superoxide dismutase (SOD) through redox cycling
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- Koizumi Rie
- Master’s Program in Environmental Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba
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- Taguchi Keiko
- Doctoral Program in Biomedical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba
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- Hisamori Miwa
- Master’s Program in Environmental Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba
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- Kumagai Yoshito
- Doctoral Program in Biomedical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba
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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
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- The Journal of Toxicological Sciences
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The Journal of Toxicological Sciences 38 (3), 317-324, 2013
一般社団法人 日本毒性学会
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詳細情報 詳細情報について
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- CRID
- 1390001204906148224
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- NII論文ID
- 10031158897
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- NII書誌ID
- AN00002808
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- COI
- 1:CAS:528:DC%2BC3sXhtVKhs7fN
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- ISSN
- 18803989
- 03881350
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- NDL書誌ID
- 024783913
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- PubMed
- 23665930
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- 使用不可