On the Role of Hydroxyl Radical and the Effect of Tetrandrine on Nuclear Factor-kappaB Activation by Phorbol 12-Myristate-13-Acetate

Details

• Personal Author:
  Ding M ; Rojanasakul Y ; Shi X ; Ye J ; Zhang X
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Acetates Alkaloids Antioxidants Chelating Agents Occupational Health Safety
• Keywords:
  Antioxidation Author Keywords: Hydroxyl Radical Chelates Free Radical Reactions Hydroxyl-groups NF-kB Phorbol Ester Superoxide Radical Tetandrine
• 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:
  65-71
• Volume:
  30
• Issue:
  1
• NIOSHTIC Number:
  nn:20020866
• Citation:
  Ann Clin Lab Sci 2000 Jan; 30(1):65-71
• Contact Point Address:
  Xianglin Shi, PhD, NIOSH, 1095 Willowdale Road, Morgantown, WV 26505
• Email:
  xas0@cdc.gov
• Federal Fiscal Year:
  2000
• 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-512:075d9636c9700be62b0fd01b49912c1f1d454790e90ea855ed594896b79f3fef52273f1f98f97f745813a5776942d605006ee9188ec8c58995536ef66b11f0a7
• Download URL:
  https://stacks.cdc.gov/view/cdc/198524/cdc_198524_DS1.pdf
• File Type:
  [PDF - 3.53 MB ]