CD95-Induced Cell Death Is Mediated by Reactive Oxygen Species

Details

• Personal Author:
  Medan D ; Mercer RR ; Rojanasakul Y ; Wang L ; Medan D ; Mercer RR ; Rojanasakul Y ; Wang L
• Description:
  Although reactive oxygen species (ROS) have long been suspected to play a key role in Fas (CD95)-induced cell death, the identity of specific ROS involved in this process and the relationship between apoptotic and necrotic cell death induced by Fas are largely unknown. Using electron spin resonance (ESR) spectroscopy, we showed that activation of Fas receptor by its ligand (FasL) in macrophages resulted in a rapid and transient production of hydrogen peroxide (H2O2) and hydroxyl radicals (.OH). The response was visible as early as 5 min and peaked at approximately 45 min post treatment with FasL. Morphological analysis of total death response showed a significant increase in apoptosis at 6 h after the treatment, while necrosis remained at a baseline level. Only at a 35-fold increase in apoptosis did necrosis become significant. Inhibition of apoptosis by a pan-caspase inhibitor, zVAD-fmk, significantly inhibited cell necrosis, indicating the linkage between the two events. Catalase (H2O2 scavenger) and deferoxamine effectively inhibited the total death response as well as the ESR signals, while superoxide dismutase (SOD) (O2.- scavenger) had minimal effects. These results established the role for H2O2 and .OH as key participants in Fas-induced cell death and indicated apoptosis as a primary mode of cell death preceding necrosis. Because the Fas death pathway is implicated in various inflammatory and immunologic disorders, utilization of antioxidants and apoptosis inhibitors as potential therapeutic agents may be advantageous. [Description provided by NIOSH]
• Subjects:
  Lung Occupational Health Respiratory System Safety
• Keywords:
  Antioxidation Cell-biology Cell-damage Cell-morphology Cellular-reactions Lung-cells
• ISSN:
  0891-5849
• Document Type:
  Text
• Genre:
  Abstract or Summary ; Abstract or Summary
• Place as Subject:
  OSHA Region 3 ; 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:
  37
• NIOSHTIC Number:
  nn:20028050
• Citation:
  Free Radic Biol Med 2004 Jan; 37(Suppl 1):S128-S129
• Federal Fiscal Year:
  2004
• Peer Reviewed:
  False
• Source Full Name:
  Free Radical Biology and Medicine
• Supplement:
  1
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:8477e5cb0020790c5e5fe9bf6907bf250579c87300154c1d4a7431d8db166f27c99fca39bd935f8ce3aeabfc7d66db8c09a371e3fea7d203c7a5836aa66c156a
• Download URL:
  https://stacks.cdc.gov/view/cdc/189750/cdc_189750_DS1.pdf
• File Type:
  [PDF - 79.25 KB ]