Detection, characterization, and decay kinetics of ROS and thiyl adducts of mito-DEPMPO spin trap

Chem Res Toxicol. 2007 Jul;20(7):1053-60. doi: 10.1021/tx700101d. Epub 2007 Jun 9.

Abstract

We report here the detection and characterization of spin adducts formed from the trapping of reactive oxygen species (superoxide and hydroxyl radicals) and glutathiyl and carbon-centered radicals by a newly synthesized nitrone, Mito-DEPMPO. This is a cationic nitrone spin trap with a triphenyl phosphonium cation conjugated to the DEPMPO analogue. The Mito-DEPMPO-OOH adduct, formed from the trapping of superoxide by Mito-DEPMPO, was enzymatically generated using xanthine/xanthine oxidase and neuronal nitric oxide synthase, and chemically generated by KO2 in 18-crown-6. The Mito-DEPMPO-OOH adduct exhibits an eight-line EPR spectrum with partial asymmetry arising from the alternate line-width effect. The half-life of the Mito-DEPMPO-OOH adduct is 2-2.5-times greater than that of the DEPMPO-OOH. The Mito-DEPMPO-SG adduct, formed from the trapping of glutathiyl radicals by Mito-DEPMPO, is 3-times more persistent than the analogue DEPMPO-SG adduct. In this study, we describe the EPR characterization of spin adducts formed from Mito-DEPMPO. The EPR parameters of Mito-DEPMPO adducts are distinctly different and highly characteristic. The detection of superoxide from an intact mitochondrion was feasible with Mito-DEPMPO but not with DEPMPO. We conclude that Mito-DEPMPO nitrone and its analogues are more effective than most nitrone spin traps for trapping superoxide, hydroxyl, and thiyl radicals formed in biological systems, including mitochondria.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Electron Spin Resonance Spectroscopy
  • Hydroxyl Radical / analysis
  • Hydroxyl Radical / chemistry*
  • Kinetics
  • Mice
  • Mitochondria / chemistry
  • Mitochondria / metabolism
  • Molecular Structure
  • Pyrroles / analysis
  • Pyrroles / chemistry*
  • Pyrroles / metabolism
  • Reactive Oxygen Species / analysis
  • Reactive Oxygen Species / chemistry*
  • Spin Trapping / methods*
  • Sulfhydryl Compounds / analysis
  • Sulfhydryl Compounds / chemistry*
  • Superoxide Dismutase / chemistry
  • Superoxide Dismutase / metabolism
  • Superoxides / analysis
  • Superoxides / chemistry*

Substances

  • (diethoxyphosphoryl)-5-methylpyrroline N-oxide
  • Pyrroles
  • Reactive Oxygen Species
  • Sulfhydryl Compounds
  • Superoxides
  • Hydroxyl Radical
  • Superoxide Dismutase