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On the role of hydroxyl radical and the effect of tetrandrine on nuclear factor-kappaB activation by phorbol 12-myristate-13-acetate.

Authors
Ye-J; Ding-M; Zhang-X; Rojanasakul-Y; Shi-X
Source
Ann Clin Lab Sci 2000 Jan; 30(1):65-71
NIOSHTIC No.
20020866
Abstract
Nuclear factor kappaB (NF-kappaB) is considered to be an important target for therapeutic intervention because of its role in the regulation of proinflammatory and profibrotic mediators. The present study examined the role of hydroxyl (OH) radical and the effect of tetrandrine, an alkaloid extracted from the Chinese medicinal herb Stephania tetrandra, on NF-kappaB activation by a tumor promoter, phorbol 12-myristate 13-acetate (PMA) in human lymphoid T cells (ie, Jurkat cells). Exogenous superoxide dismutase (SOD) enhanced the NF-kappaB activation by PMA, while catalase blocked it. Formate, a scavenger of OH radical, also was inhibitory, as was deferoxamine, a metal chelator. These data suggest an important role of OH radical in PMA-induced NF-kappaB activation. Incubation of the cells with tetrandrine prior to the stimulation of the cells was found to inhibit PMA-induced NF-kappaB activation. Tetrandrine activity was so potent that 50 microM of tetrandrine was sufficient to inhibit activation of NF-kappaB completely. Electron spin resonance (ESR) spin trapping was used to investigate the antioxidant action of tetrandrine using 5,5-dimethyl-1-pyrroline N-oxide (DMPO) as a spin trap. Tetrandrine is an antioxidant for both OH and superoxide (O2-)radicals. The reaction rate constant of tetrandrine with OH is 1.4 x 10(10) M(-1)sec(-1), which is comparable with several well established antioxidants, such as ascorbate, glutathione, and cysteine. The Fenton reaction (Fe(II) + H2O2-->Fe(III) + OH + OH-) and xanthine/xanthine oxidase were used as sources of OH and O2- radicals. The free radical scavenging activity of tetrandrine is responsible for its inhibition of PMA-induced NF-kappaB activation.
Keywords
Acetates; Alkaloids; Hydroxyl-groups; Chelates; Antioxidants; Antioxidation
Contact
Xianglin Shi, PhD, NIOSH, 1095 Willowdale Road, Morgantown, WV 26505
CODEN
ACLSCP
Publication Date
20000101
Document Type
Journal Article
Email Address
xas0@cdc.gov
Fiscal Year
2000
NTIS Accession No.
NTIS Price
Issue of Publication
1
ISSN
0091-7370
NIOSH Division
HELD
Source Name
Annals of Clinical and Laboratory Science
State
WV
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