Involvement of Protein Kinase C in Crystalline Silica-Induced Activation of the MAP Kinase and AP-1 Pathway

Details

• Personal Author:
  Bowman L ; Castranova, Vincent ; Ding M ; Huang C ; Lu YJ ; 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 PKCalpha and PKCepsilon 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, overexpression of dominant negative mutant (DNM) of PKCalpha or PKCepsilon markedly blocked AP-1 activation as well as phosphorylation of ERKs and p38 kinase induced by freshly fractured silica. These results demonstrate that PKCalpha and PKCepsilon are essential in silica-induced AP-1 activation through the MAP kinase (ERKs and p38 kinases) pathway. [Description provided by NIOSH]
• Subjects:
  Aluminum Silicates Animals Carcinogens Dust Laboratories Occupational Health Quartz Safety Silicon Dioxide
• Keywords:
  Animal-studies Carcinogenesis Carcinogenicity Fibrogenesis Fibrogenicity Laboratory-animals Quartz-dust Silica-dusts Silicates
• ISSN:
  1040-0605
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  New York ; OSHA Region 2 ; 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:
  290
• Issue:
  2
• NIOSHTIC Number:
  nn:20029338
• Citation:
  Am J Physiol Lung Cell Mol Physiol 2006 Feb; 290(2):L291-L297
• Contact Point Address:
  M. Ding, PPRB, NIOSH, 1095 Willowdale Rd., Morgantown, WV 26505
• Email:
  mid5@cdc.gov
• 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:
  True
• Source Full Name:
  American Journal of Physiology: Lung Cellular and Molecular Physiology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:3838160ac607a6b59827c77b35fb4570fc614632cd1afadc09036083a46860afe05db67301a2af145aa6eeabb06bc47e6343bf6bb7b8e697d0363d9becb08d68
• Download URL:
  https://stacks.cdc.gov/view/cdc/190340/cdc_190340_DS1.pdf
• File Type:
  [PDF - 301.38 KB ]