Superoxide generation mediated by 8-nitroguanosine, a highly redox-active nucleic acid derivative

Tomohiro Sawa, Takaaki Akaike, Koji Ichimori, Teruo Akuta, Kazuyoshi Kaneko, Hitoshi Nakayama, Dennis J. Stuehr, Hiroshi Maeda

Research output: Contribution to journalArticlepeer-review

50 Citations (Scopus)

Abstract

Formation of 8-nitroguanosine may be characterized as nucleic acid modification induced by nitric oxide (NO). We show here that 8-nitroguanosine is a highly redox-active nucleic acid derivative that strongly stimulated superoxide generation from various NADPH-dependent reductases, including cytochrome P450 reductase and all isoforms of NO synthase. This reaction involves these reductases in a redox cycling reaction via single-electron reduction of 8-nitroguanosine to form 8-nitroguanosine anion radical. One electron is then transferred from this radical to molecular oxygen. 8-Nitroguanosine formed in vivo may function as a potent redox cofactor that intensifies oxyradical generation by various NADPH/reductase-like enzymes and thus participates in diverse physiological and pathological events.

Original languageEnglish
Pages (from-to)300-306
Number of pages7
JournalBiochemical and biophysical research communications
Volume311
Issue number2
DOIs
Publication statusPublished - 2003 Nov 14
Externally publishedYes

Keywords

  • 8-Nitroguanosine
  • NADPH-dependent reductase
  • Nitrative stress
  • Nitric oxide
  • Nitric oxide synthase
  • Reactive nitrogen oxides
  • Superoxide

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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