Freshly Fractured Crystalline Silica Induces Activator Protein-1 Activation Through ERKs and p38 MAPK

Details

• Personal Author:
  Castranova C ; Chen F ; Ding M ; Dong Z ; Lu Y ; Shi X ; Vallyathan V
• Description:
  The transcription factor activator protein-1 (AP-1) reportedly plays an important role in the induction of neoplastic transformation and multiple genes involved in cell proliferation, differentiation, and inflammation. To investigate the mechanisms of silica-induced carcinogenesis, AP-1-luciferase reporter transgenic mice were used as an in vivo model, whereas the JB6 mouse epidermal cell line and a rat lung epithelial cell line were employed as in vitro models to study the effects of silica at the molecular level. Freshly fractured silica caused an 8-fold increase in AP-1 activity in JB6 cells and a 2.5-fold increase in rat lung epithelial cells. The induction of AP-1 activity in cultured cell lines was time- and dose-dependent. Intratracheal administration of silica was also able to induce AP-1 transactivation in transgenic mice. AP-1 activation was first observed at 2 days after silica administration and reached its maximum at 3 days post-exposure of the mice to silica. The signal transduction pathways for AP-1 activation were also investigated using these cell lines. The results demonstrate that freshly fractured silica stimulates mitogen-activated protein kinase (MAPK) family members, as determined by the phosphorylation of p38 MAPK and extracellular signal-regulated protein kinases (ERKs). Inhibition of ERKs with PD98059 or of p38 with SB203580 significantly inhibited silica-induced AP-1 activation. These findings demonstrate for the first time that freshly fractured silica induces AP-1 activation, which may be mediated through p38 MAPK and ERK pathways. Unraveling the complex mechanisms associated with these events may provide insights into the initiation and progression of silica-induced carcinogenesis. [Description provided by NIOSH]
• Subjects:
  Aluminum Silicates Animals Dust Fibrosis Inhalation Exposure Laboratories Lung Lung Diseases Occupational Health Quartz Respiratory System Respiratory Tract Diseases Safety Silicon Dioxide

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• Keywords:
  Animal-studies Cell-damage Dust-exposure Dust-inhalation Dust-particles Inhalants Laboratory-animals Lung-disease Lung-function Pulmonary-system-disorders Quartz-dust Respiratory-system-disorders Silica-dusts Silicates

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• ISSN:
  0021-9258
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Minnesota ; OSHA Region 3 ; OSHA Region 5 ; 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:
  274
• Issue:
  43
• NIOSHTIC Number:
  nn:20027728
• Citation:
  J Biol Chem 1999 Oct; 274(43):30611-30616
• Contact Point Address:
  V. Vallyathan, Pathology and Physiology Research Branch, NIOSH, 1095 Willowdale Rd., Morgantown, WV 26505
• Email:
  vav1@cdc.gov
• CAS Registry Number:
  Quartz (SiO2) (CAS RN 14808-60-7)
• Federal Fiscal Year:
  2000
• Peer Reviewed:
  True
• Source Full Name:
  Journal of Biological Chemistry
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:42b60c1b05a2c4a1e4e6822823600363610db577894d095fc016ef7ce17dad76dd87b06ee818ac90c4e126b0439445c8b2980bb3d20dc8450faae88b55a1a5d0
• Download URL:
  https://stacks.cdc.gov/view/cdc/197642/cdc_197642_DS1.pdf
• File Type:
  [PDF - 182.73 KB ]