The role of superoxide radical in TNF-α induced NF-κB activation

Suwei Wang, Stephen S. Leonard, Vince Castranova, Val Vallyathan, Xianglin Shi

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

Electron spin resonance (ESR) spin trapping with 5- (diethoxyphosphoryl)-5-methyl-1-pyrroline N-oxide (DEPMPO) was utilized to investigate the generation of oxygen free radicals from macrophages stimulated by tumor necrosis factor-α (TNF-α). TNF-α stimulated macrophages generated hydroxyl (·OH) and superoxide anion (O2.-) radicals. Incubation of TNF-α with macrophages resulted in an activation of DNA binding activity of the nuclear transcription factor NF-κB. Superoxide dismutase (SOD), but not catalase or sodium formate, inhibited this NF-κB activation, suggesting that O2.- rather than H2O2 or ·OH, radicals play the most critical role in this induction. β-Nicotinamide adenine dinucleotide phosphate (NADPH) did not affect the NF-κB activation, while allopurinol, an inhibitor of xanthine oxidase, repressed it, suggesting that xanthine/xanthine oxidase, and not NADPH dependent oxidase, may be a source of O2.- radicals which induce NF-κB activation. O2.- is generated via reduction of molecular oxygen by xanthine and xanthine oxidase, as demonstrated by the oxygen consumption assay. The results indicate that TNF- α induces oxygen radical generation from macrophages. O2.- seems to play a key role in TNF-α-induced NF-κB activation in macrophages. Xanthine and xanthine oxidase appears to be a source of O2.- radicals responsible for TNF-α-induced NF-κB activation.

Original languageEnglish
Pages (from-to)192-199
Number of pages8
JournalAnnals of Clinical and Laboratory Science
Volume29
Issue number3
StatePublished - 1999

ASJC Scopus subject areas

  • Microbiology
  • Immunology and Allergy
  • Pathology and Forensic Medicine
  • Immunology
  • Molecular Biology
  • Hematology
  • Clinical Biochemistry
  • Medical Laboratory Technology

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