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

Rie Koizumi, Keiko Taguchi, Miwa Hisamori, Yoshito Kumagai

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)317-324
Number of pages8
JournalJournal of Toxicological Sciences
Volume38
Issue number3
DOIs
Publication statusPublished - 2013 Jun
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Toxicology

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