Induction of Activator Protein-1 Through Reactive Oxygen Species by Crystalline Silica in JB6 Cells

Details

• Personal Author:
  Antonini J ; Castranova, Vincent ; Ding M ; Huang C ; Leonard, Stephanie ; Lu Y ; Roberts J ; Shi X ; Vallyathan V
• Description:
  We reported previously that freshly fractured silica (FFSi) induces activator protein-1 (AP-1) activation through extracellular signal-regulated protein kinases (ERKs) and p38 kinase pathways. In the present study, the biologic activities of FFSi and aged silica (ASi) were compared by measuring their effects on the AP-1 activation and phosphorylation of ERKs and p38 kinase. The roles of reactive oxygen species (ROS) in this silica-induced AP-1 activation were also investigated. We found that FFSi-induced AP-1 activation was four times higher than that of ASi in JB6 cells. FFSi also caused greater phosphorylation of ERKs and p38 kinase than ASi. FFSi generated more ROS than ASi when incubated with the cells as measured by electron spin resonance (ESR). Studies using ROS-sensitive dyes and oxygen consumption support the conclusion that ROS are generated by silica-treated cells. N-Acetylcysteine (an antioxidant) and polyvinyl pyridine-N-oxide (an agent that binds to Si-OH groups on silica surfaces) decreased AP-1 activation and phosphorylation of ERKs and p38 kinase. Catalase inhibited phosphorylation of ERKs and p38 kinase, as well as AP-1 activation induced by FFSi, suggesting the involvement of H(2)O(2) in the mechanism of silica-induced AP-1 activation. Sodium formate (an ( small middle dot)OH scavenger) had no influence on silica-induced MAPKs or AP-1 activation. Superoxide dismutase enhanced both AP-1 and MAPKs activation, indicating that H(2)O(2), but not O(2), may play a critical role in silica-induced AP-1 activation. These studies indicate that freshly ground silica is more biologically active than aged silica and that ROS, in particular H(2)O(2), play a significant role in silica-induced AP-1 activation. [Description provided by NIOSH]
• Subjects:
  Aluminum Silicates Animals Laboratories Lung Lung Diseases Neoplasms Occupational Health Respiratory System Respiratory Tract Diseases Safety Silicon Dioxide

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• Keywords:
  Animal-studies Cancer Exposure-levels Laboratory-animals Lung-cancer Silica-dusts Silicates Silicosis
• ISSN:
  0021-9258
• Document Type:
  Text
• Genre:
  Journal Article
• 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:
  276
• Issue:
  12
• NIOSHTIC Number:
  nn:20021716
• Citation:
  J Biol Chem 2001 Mar; 276(12):9108-9114
• Contact Point Address:
  Pathology and Physiology Research Branch, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505
• Email:
  vav1@cdc.gov
• CAS Registry Number:
  Quartz (SiO2) (CAS RN 14808-60-7)
• Federal Fiscal Year:
  2001
• 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:a8b909b936c0d6db47ecbbaff8e68b37e0db05ec69a2005eaebba44222ab894c5aa3aef07eea5831a130fc3d619962c581e216ce412a262a0b933372b877ead8
• Download URL:
  https://stacks.cdc.gov/view/cdc/198831/cdc_198831_DS1.pdf
• File Type:
  [PDF - 742.10 KB ]