The Involvement of Mitochondria in Silica-Induced Apoptosis of Pulmonary Phagocytes

Details

• Personal Author:
  Barger M ; Hu S ; Ma JK ; Ma JYC
• Description:
  We have previously shown that silica particles, a ubiquitous occupational fibrogenic agent that induces inflammatory responses through microtubule alterations, may activate caspase cascade leading to cell apoptosis. The purpose of this study is to investigate the potential involvement of mitochondria in silica-induced apoptosis. Rats were intratracheally instilled with saline or silica (20mg/kg) particles and were sacrificed 3 days post-exposure. Alveolar macrophages (AMs) were harvested by bronchoalveolar lavage. Apoptosis was measured by cell death detection ELISA with or without microtubule modifiers (taxol or tetrandrine). Intracellular generation of reactive oxygen species (ROS) was assayed by using confocal microscopy. Mitochondrial trans-membrane potential was examined using Jc-1 staining. Mitochondrial release of Cytochrome c and the resulting activation of caspase-9 and caspase-3 were determined by Western blots. Silica particles increased the intracellular generation of ROS as compared to saline control. This effect was enhanced by microtubule modifiers taxol and tetrandrine. Silica along with the microtubule modifiers caused mitochondrial membrane depolarization and cytochrome c release. Caspase-9 and caspase3 were also induced by the silica treatment. The results show that silica particles induce AM apoptosis that involves alteration of microtubule structure and the activation of the mitochondria by oxygen radicals. [Description provided by NIOSH]
• Subjects:
  Aluminum Silicates Animals Laboratories Occupational Health Safety Silicon Dioxide
• Keywords:
  Animal Studies Cell Damage Laboratory Animals Microscopy Phagocytes Silica Dusts Silicates
• ISSN:
  1522-1059
• Publisher:
  American Association of Pharmaceutical Scientists
• 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:
  4
• Issue:
  4
• NIOSHTIC Number:
  nn:20023587
• Citation:
  AAPS Pharm Sci 2002 Jan; 4(4):M1086
• Federal Fiscal Year:
  2002
• Peer Reviewed:
  False
• Source Full Name:
  AAPS Pharmaceutical Sciences
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:3a1ef86023449a9e8dc86e7dfe27ad86a27e620cca6c8c209618cb9df5c45046cdcb2b3947983ffd465b70440c034177eac6eb254724654a0e7f150de7a7868e
• Download URL:
  https://stacks.cdc.gov/view/cdc/195935/cdc_195935_DS1.pdf
• File Type:
  [PDF - 156.88 KB ]