Activation of Protein Kinase C Is Required for Silica-Induced Activation of the MAP Kinase-AP-1 Pathway

Details

• Personal Author:
  Bowman L ; Castranova, Vincent ; Ding M ; Huang C ; Lu Y ; Bowman L ; Castranova, Vincent ; Ding M ; Huang C ; Lu Y
• Description:
  Silica particles are considered to be fibrogenic agents and have been recently designated as carcinogenic, but the mechanisms for cancer initiation and progression are not well understood. By using an AP-1-luciferase reporter cell line, we demonstrated that activator protein-1 (AP-1) activation by crystalline silica is through mitogen-activated protein kinases (MAPK), i.e.,ERKs and p38 kinases. The present study investigates the role of protein kinase C (PKC) in silica-induced activation of the MAPK-AP-1 pathway. Treatment of JB6 cells with freshly fractured silica stimulated translocation of PKC*, PKC*, and PKC, from the cytosol to the membrane and activated Ap-1 activity. Rotterin (a selective inhibitor of PKC*), RO-32-0432 (a relative specific inhibitor for PKC), and calphostic C and bisindolylmaleimide I (general PKC inhibitors for all the subtypes), inhibited silica-stimulated AP-1 actication. These effects of PKC inhibitors were dose dependent. Dominate negative mutant transfectants of PKC markedly blocked AP-1 activation induced by silica. Western blot analysis using phosphor-specific antibodies indicates that PKC inhibitors or dominant negative mutant transfectants of PKC also blocked silica-induced phosphor ylation of ERKs and p38 kinase. Thses results demonstrate that PKC", PKC*, and PKC, mediate silica induced AP-1 activation through MAP kinase (ERKs and p38 kinases) pathways. [Description provided by NIOSH]
• Subjects:
  Aluminum Silicates Irritants Lung Lung Diseases Occupational Health Respiratory System Respiratory Tract Diseases Safety Silicon Dioxide
• Keywords:
  Cell-damage Cellular-reactions Fibrogenicity Pulmonary-disorders Pulmonary-function Pulmonary-system-disorders Respiratory-irritants Respiratory-system-disorders Silica-dusts Silicates Silicosis

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• ISSN:
  0025-7818
• Document Type:
  Text
• Genre:
  Abstract or Summary ; Proceedings ; Abstract or Summary ; Proceedings
• Place as Subject:
  New York ; Ohio ; OSHA Region 2 ; OSHA Region 3 ; OSHA Region 5 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH) ; National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division ; HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health ; Workplace Safety & Health
• Location:
  North America ; North America
• Volume:
  93
• NIOSHTIC Number:
  nn:20027145
• Citation:
  Med Lav 2002 Oct; 93(Suppl):S41
• CAS Registry Number:
  Quartz (SiO2) (CAS RN 14808-60-7) ; Silica (CAS RN 7631-86-9) ; Quartz (SiO2) (CAS RN 14808-60-7) ; Silica (CAS RN 7631-86-9)
• Federal Fiscal Year:
  2003
• Peer Reviewed:
  False
• Source Full Name:
  La Medicina del Lavoro. 3rd International Symposium on Silica, Silicosis, Cancer and Other Diseases, S. Margherita Ligure, 21-25 October 2002
• Supplement:
  Suppl
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:5718e65b714d64c3dfcb25e283222091e9aa4194c9e2ab5b816d2ea42d8679284cec6a1b4e4070941a9bf72e809926fb5f675c86c547bde8a1fca512a9f2d4b6
• Download URL:
  https://stacks.cdc.gov/view/cdc/197478/cdc_197478_DS1.pdf
• File Type:
  [PDF - 1.54 MB ]