Involvement of Hydrogen Peroxide in Asbestos-Induced NFAT Activation

Details

• Personal Author:
  Castranova, Vincent ; Huang B ; Huang C ; Li J ; Shi X ; Vallyathan V
• Description:
  The present study investigated the role of reactive oxygen species (ROS) in activation of nuclear factor of activated T cells (NFAT), a pivotal transcription factor responsible for regulation of cytokines, by asbestos in mouse embryo fibroblast PW cells. Exposure of cells to asbestos led to the transactivation of NFAT in a time- and dose-dependent manner. Scavenging of asbestos-induced H2O2 with N-acety-L-cyteine (NAC, a general antioxidant) or catalase (a specific H2O2 inhibitor) resulted in inhibition of NFAT activation. In contrast, an increase in H2O2 generation by the addition of superoxide dismutase (SOD) slightly enhanced asbestos-induced NFAT activation. In addition, pretreatment of cells with sodium formate did not exhibit any inhibition of NFAT activity induced by asbestos. These results demonstrated that H2O2 appeared to play an important role in asbestos-induced NFAT transactivation. Furthermore, it was observed that incubation of cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) not only resulted in NFAT activation by itself, but also enhanced asbestos-induced NFAT induction. Pretreatment of cells with cyclosporin A (CSA), a pharmacological inhibitor of the phosphatase calcineurin, blocked both asbestos- and TPA plus asbestos-induced NFAT activation. These data suggest that asbestos is able to induce NFAT activation through H2O2-dependent and CSA-sensitive pathways, which may be involved in asbestos-induced carcinogenesis. [Description provided by NIOSH]
• Subjects:
  Animals Asbestos Inorganic Chemicals Occupational Health Safety
• Keywords:
  Animal-studies Asbestos Author Keywords: Reactive Oxygen Species Cell-alteration Cell-function Dose-response In-vitro-study NFAT
• ISSN:
  0300-8177
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Maryland ; 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:
  161-168
• Volume:
  234
• Issue:
  1
• NIOSHTIC Number:
  nn:20022959
• Citation:
  Mol Cell Biochem 2002 May; 234-235(1-2):161-168
• Contact Point Address:
  Nelson Institute of Environmental Medicine, New York University School of Medicine, 57 Old Forge Road,Tuxedo 10987, USA
• Email:
  chuanshu@env.med.nyu.edu
• Federal Fiscal Year:
  2002
• NORA Priority Area:
  Research Tools and Approaches: Cancer Research Methods
• Peer Reviewed:
  True
• Source Full Name:
  Molecular and Cellular Biochemistry
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:04001e6e0f0bc963a0306a24ca1bc5111a61249ebb7dfdd33ad495982d7a7b1e8f845e2fb756400cb2e0a35f4580d0d392fad14084c9725900a66ed6566cda0c
• Download URL:
  https://stacks.cdc.gov/view/cdc/199563/cdc_199563_DS1.pdf
• File Type:
  [PDF - 139.55 KB ]