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The role of superoxide radical in TNF-alpha induced NF-kappaB activation.

Authors
Wang-S; Leonard-SS; Castranova-V; Vallyathan-V; Shi-X
Source
Ann Clin Lab Sci 1999 Jul; 29(3):192-199
NIOSHTIC No.
20000964
Abstract
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.
Keywords
In-vitro-studies; Cancer; Analytical-methods; Proteins; Enzymes; Genetics
Contact
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
CODEN
ACLSCP
Publication Date
19990701
Document Type
Journal Article
Email Address
xasO@cdc.gov
Fiscal Year
1999
NTIS Accession No.
NTIS Price
Issue of Publication
3
ISSN
0091-7370
NIOSH Division
HELD
Priority Area
Cancer Research Methods; Research Tools and Approaches
Source Name
Annals of Clinical and Laboratory Science
State
WV
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