Essential Role of Protein Kinase C in Silica-Induced Map Kinase and AP-1 Activation

Details

• Personal Author:
  Bowman L ; Castranova, Vincent ; Ding M ; Lu Y ; Vallyathan V
• Description:
  Crystalline silica has long been well established as a fibrogenic agent and recent evidence has implicated it as a potential human carcinogen. However, the mechanisms of silica-induced disease development and progression are not well understood. Our previous studies demonstrated that crystalline silica is able to activate activator protein-1 (AP-1) through mitogen-activated protein kinase (MAPK) pathways. The present study investigates the possible involvement of protein kinase C (PKC) in silica-induced activation of the MAPK-AP-1 signal transduction pathway. Treatment of mouse epidermal cells (JB6 cell line) with freshly fractured silica stimulated translocation of PKCa and PKCe from the cytosol to the membrane and activated AP-1 transcription activity. Pretreatment of cells with PKC inhibitors, including RO-32-0432, calphostin C, and bisindolylmaleimide I, inhibited silica-induced AP-1 activation and phosphorylation of ERKs and p38 kinase. These inhibitory effects by PKC inhibitors were dose dependent. Furthermore, over-expression of a dominant negative mutant of PKCa or PKCe markedly blocked AP-1 activation as well as phosphorylation of ERKs and p38 kinase induced by freshly fractured silica. These results demonstrate that PKCa and PKCe are essential in silica-induced AP-1 activation through the MAP kinase (ERKs and p38 kinases) pathway. [Description provided by NIOSH]
• Subjects:
  Aluminum Silicates Carcinogens Dust Occupational Health Quartz Safety Silicon Dioxide
• Keywords:
  Carcinogenesis Carcinogenicity Fibrogenesis Fibrogenicity Proteins Quartz-dust Silica-dusts Silicates Silicosis
• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• 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
• Volume:
  90
• Issue:
  1
• NIOSHTIC Number:
  nn:20029884
• Citation:
  Toxicologist 2006 Mar; 90(1):208
• CAS Registry Number:
  Quartz (SiO2) (CAS RN 14808-60-7)
• Federal Fiscal Year:
  2006
• NORA Priority Area:
  Research Tools and Approaches: Cancer Research Methods
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 45th Annual Meeting and ToxExpo, March 5-9, 2006, San Diego, California
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:e893dea9bf549d355c3637e2be30ff08c53a6a38dd76085b792bafbc61cf65d564a603d41b5228e24c1b919137d9be3071abca039389da9c41b1ebd38007a9e8
• Download URL:
  https://stacks.cdc.gov/view/cdc/190778/cdc_190778_DS1.pdf
• File Type:
  [PDF - 151.43 KB ]