Inhibitor of Nuclear Factor kB Kinase Deficiency Enhances Oxidative Stress and Prolongs C-Jun NH2-Terminal Kinase Activation Induced by Arsenic

Details

• Personal Author:
  Castranova, Vincent ; Chen F ; Karin M ; Li Z ; Shi X
• Description:
  Stress signals activate both inhibitor of nuclear factor-kappaB kinase (IKKbeta) and c-Jun NH(2)-terminal kinase (JNK). It was shown recently that IKK-dependent nuclear factor kappaB activation results in attenuation of tumor necrosis factor alpha-induced JNK activation. How that negative cross-talk between nuclear factor kappaB and JNK occurs is not well-understood. By using wild-type and Ikkbeta gene knockout (Ikkbeta(-/-)) mouse embryo fibroblasts, we found that IKKbeta deficiency results in prolongation of arsenic-induced JNK activation, which was not due to the decreased expression of GADD45beta or X-linked Inhibitor of Apoptosis (XIAP), as suggested previously for RelA(-/-) cells treated with tumor necrosis factor alpha. This enhanced JNK activation was largely associated with an oxidative stress response as indicated by elevated expression of heme oxygenase-1 and the accumulation of H(2)O(2) in Ikkbeta(-/-) cells. Expression profiling experiments revealed an increased expression of p450 family CYP1B1 mRNA in Ikkbeta(-/-) cells compared with wild-type cells. Inhibition of CYP1B1 reduced both oxidative stress and arsenic-stimulated JNK activation. Thus, increased CYP1B1 expression is central to and seems to be responsible for sensitizing Ikkbeta(-/-) cells to stress-induced JNK activation. [Description provided by NIOSH]
• Subjects:
  Animals Arsenic Hydrocarbons Hypersensitivity Inorganic Chemicals Laboratories Occupational Health Safety
• Keywords:
  Animal-studies Arsenic-compounds Laboratory-animals Oxidative-processes Sensitization Stress
• ISSN:
  0008-5472
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  California ; OSHA Region 3 ; OSHA Region 9 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  63
• Issue:
  22
• NIOSHTIC Number:
  nn:20023885
• Citation:
  Cancer Res 2003 Nov; 63(22):7689-7693
• Contact Point Address:
  Fei Chen, Health Effects Laboratory Division, NIOSH, PPRB, 1095 Willowdale Road, Morgantown, WV 26505
• CAS Registry Number:
  Arsenic (CAS RN 7440-38-2)
• Federal Fiscal Year:
  2004
• Peer Reviewed:
  True
• Source Full Name:
  Cancer Research
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:d5b7d225378b1f99cbca47e1ab18d14b538205f194a36fdca8f51acac10042d922e05005e56b5cf63820003b54c0a92afe5123a9581f13a032111e60ff8ee426
• Download URL:
  https://stacks.cdc.gov/view/cdc/195967/cdc_195967_DS1.pdf
• File Type:
  [PDF - 393.45 KB ]