Cobalt-mediated generation of reactive oxygen species and its possible mechanism

Stephen Leonard, Peter M. Gannett, Yon Rojanasakul, Diane Schwegler-Berry, Vince Castranova, Val Vallyathan, Xianglin Shi

Research output: Contribution to journalArticlepeer-review

159 Scopus citations

Abstract

Electron spin resonance spin trapping was utilized to investigate free radical generation from cobalt (Co) mediated reactions using 5,5-dimethyl-1- pyrroline (DMPO) as a spin trap. A mixture of Co with water in the presence of DMPO generated 5,5-dimethylpyrroline-(2)-oxy(1) DMPOX, indicating the production of strong oxidants. Addition of superoxide dismutase (SOD) to the mixture produced hydroxyl radical (·OH). Catalase eliminated the generation of this radical and metal chelators, such as desferoxamine, diethylenetriaminepentaacetic acid or 1,10-phenanthroline, decreased it. Addition of Fe(II) resulted in a several fold increase in the ·OH generation. UV and O2 consumption measurements showed that the reaction of Co with water consumed molecular oxygen and generated Co(II). Since reaction of Co(II) with H2O2 did not generate any significant amount of ·OH radicals, a Co(I) mediated Fenton-like reaction [Co(I) + H2O2 → Co(II) + ·OH + OH-] seems responsible for ·OH generation. H2O2 is produced from O2/.- via dismutation. O2/.- is produced by one-electron reduction of molecular oxygen catalyzed by Co. Chelation of Co(II) by biological chelators, such as glutathione or β-ananyl-3-methyl-L-histidine alters, its oxidation-reduction potential and makes Co(II) capable of generating ·OH via a Co(II)-mediated Fenton-like reaction [Co(II) + H2O2 → Co(III) + ·OH + OH-]. Thus, the reaction of Co with water, especially in the presence of biological chelators, glutathione, glycylglycylhistidine and β-ananyl-3- methyl-L-histidine, is capable of generating a whole spectrum of reactive oxygen species, which may be responsible for Co-induced cell injury.

Original languageEnglish
Pages (from-to)239-244
Number of pages6
JournalJournal of Inorganic Biochemistry
Volume70
Issue number3-4
DOIs
StatePublished - Jul 1998

Keywords

  • Cell injury
  • Cobalt
  • Mechanism
  • Reactive oxygen species

ASJC Scopus subject areas

  • Biochemistry
  • Inorganic Chemistry

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