The Role of Superoxide Radical in TNF-Alpha Induced NF-kappaB Activation

Details

• Personal Author:
  Castranova, Vincent ; Leonard, Stephen S. ; Shi X ; Vallyathan V ; Wang S
• Description:
  Electron spin resonance (ESR) spin trapping with 5-(diethioxyphosphoyl)-5-methyl-1-pyrroline N-oxide (DEPMPO) was utilized to investigate the generation of oxygen free radicals from macrophages stimulated by tumor necrosis factor-alpha (TNF-alpha). TNF-alpha stimulated macrophages generated hydroxyl (*OH) and superoxide anion (O2*-) radicals. Incubation of TNF-alpha with macrophages resulted in an activation of DNA binding activity of the nuclear transcription factor NF-kappaB. Superoxide dismutase (SOD), but not catalase or sodium formate, inhibited this NF-kappaB activation, suggesting that O2*- rather than H2O2 or *OH, radicals play the most critical role in this induction. beta-Nicotinamide adenine dinucleotide phosphate (NADPH) did not affect the NF-kappaB 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-kappaB activation. 02*-is generated via reduction of molecular oxygen by xanthine and xanthine oxidase, as demonstrated by the oxygen consumption assay. The results indicate that TNF-alpha induces oxygen radical generation from macrophages. 02*- seems to play a key role in TNF-alpha-induced NF-kappaB activation in macrophages. Xanthine and xanthine oxidase appears to be a source of O2*- radicals responsible for TNF-alpha-induced NF-kappaB activation. [Description provided by NIOSH]
• Subjects:
  Enzymes Genetics Neoplasms Occupational Health Safety
• Keywords:
  Analytical-methods Cancer In-vitro-studies Proteins
• ISSN:
  0091-7370
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  192-199
• Volume:
  29
• Issue:
  3
• NIOSHTIC Number:
  nn:20000964
• Citation:
  Ann Clin Lab Sci 1999 Jul; 29(3):192-199
• Contact Point Address:
  to: Xianglin Shi, Ph.D., Pathology and Physiology Research Branch, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Mail Stop B167, Morgantown WV 26505
• Email:
  xasO@cdc.gov
• Federal Fiscal Year:
  1999
• NORA Priority Area:
  Research Tools and Approaches: Cancer Research Methods
• Peer Reviewed:
  True
• Source Full Name:
  Annals of Clinical and Laboratory Science
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:215a43016dd58876c0cc05117d46d041046dddcaa3fc42c4a6f941e42f47cd9c66702d5fab0fa0ed0577d611b325a205974cfebbf5929c96b76d38608b6c57cb
• Download URL:
  https://stacks.cdc.gov/view/cdc/198276/cdc_198276_DS1.pdf
• File Type:
  [PDF - 1.66 MB ]