The Role of Hydroxyl Radical as a Messenger in the Activation of Nuclear Transcription Factor NFKB

Details

• Personal Author:
  Castranova, Vincent ; Chen F ; Ding M ; Dong Z ; Huang C ; LeonardSS ; Liu K ; Ma W ; Shi X ; Vallyathan V ; Ye J
• Description:
  Although it is generally believed that reactive oxygen species activate NF-KB, a primary oxidative stress-responsive transcription factor, it is unclear which one among these species causes NF-KB activation. Our hypothesis is that hydroxyl radical (·OH) functions as a messenger for the activation of NF-KB. Jurkat cells, macrophages and JB6 cells were used to test this hypothesis. Cr(VI), silica and ZnO were used as sources of ·OH radicals. None of these ·OH generating systems involves exogenous H2O2. Cr(VI) expressed enhanced activity in induction of NF-KB in Jurkat cells. This activation of NF-B was decreased by a metal chelator, diethylene triaminepentaacetic acid or a H2O2 scavenger, catalase, but was increased by superoxide dismutase. Mn(II), which reacts with Cr(IV) to inhibit this metal ion-mediated ·OH generation, decreased the NF-B activation. Sodium formate, an ·OH radical scavenger, also inhibited the NF-B activation. Electron spin resonance measurements show that Cr(VI) was reduced by Jurket cells to Cr(IV) and Cr(V). During the reduction process, molecular oxygen was reduced to O2- and then to H2O2, which reacted with Cr(IV) and Cr(V) to generate ·OH radical. The ·OH generation correlated with the Cr(VI)-induced NF-KB activation. Similarly, silica caused NF-KB activation in macrophages via the ·OH radical-mediated reaction. This radical was generated via metal mediated reaction from H2O2, which was generated by the reduction of molecular oxygen via O2- as an intermediate during the silica-stimulated respirable burst. Silica particles did not cause ·OH generation either in Jurket or in JB6 cells and thus did not cause any observable NF-KB activation in these cells. ZnO induced NF-KB activation in JB6 cells through the generation of ·OH resulting from light irradiation of ZnO which was measured by electron spin resonance. The results thus show that ·OH radical functions as a messenger for NF-KB activation. Antioxidants, which scavenge ·OH radical or its precursors, inhibit NF-KB activation. Metal chelators, which make metal ions incapable of generating ·OH from H2O2, inhibit activation of this transcription factor. [Description provided by NIOSH]
• Subjects:
  Antioxidants Cells, Cultured Occupational Health Safety
• Keywords:
  Antioxidation Cell-cultures Cell-damage Cell-transformation Cellular-reactions Hydroxy-compounds Hydroxyl-groups Hydroxylation-reactions Metallic-ions Nuclear-resonance
• ISSN:
  0300-8177
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Minnesota ; OSHA Region 3 ; OSHA Region 5 ; 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:
  63-70
• Volume:
  194
• Issue:
  1
• NIOSHTIC Number:
  nn:20027716
• Citation:
  Mol Cell Biochem 1999 Apr; 194(1):63-70
• Contact Point Address:
  X. Shi, Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA
• CAS Registry Number:
  Chromic trioxide (CAS RN 1333-82-0) ; Chromium(6+) (CAS RN 18540-29-9) ; Ferrous oxide (CAS RN 1345-25-1) ; Zinc oxide (ZnO) (CAS RN 1314-13-2)
• Federal Fiscal Year:
  1999
• Peer Reviewed:
  True
• Source Full Name:
  Molecular and Cellular Biochemistry
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:e65a98f5c7ef0937933da0d9f8941cb026d9789d577b71f03a7c728bd5cdcf4827317ac780d53e844f842576ea39169952b538ad56788993e4e5e7ffd0489772
• Download URL:
  https://stacks.cdc.gov/view/cdc/197638/cdc_197638_DS1.pdf
• File Type:
  [PDF - 74.65 KB ]