A combination of antiapoptotic/antinecroptotic inhibitors protects nccit cells from gamma-irradiation-induced cell death

Details

• Personal Author:
  Bayir H ; Greenberger J ; Huang Z ; Kagan V ; Bayir H ; Greenberger J ; Huang Z ; Kagan V
• Description:
  Irradiation-induced cell death includes apoptotic and necroptotic (or programmed necrosis) pathways. Therefore, a search for radiomitigators with the delayed action against acute radiation injury due to radionuclide release in terrorist acts may be based on a combination of antiapoptotic and antinecroptotic inhibitors. Here we used a cocktail that included a pan-capase inhibitor, Z-VAD-fmk, and necrostatin- 1, a specific inhibitor of receptor interacting protein-1 (RIP-1) - a key protein in necroptosis - and assessed their protective effects against irradiation-induced (4 Gy) death of embryonic carcinoma NCCIT cells (5 days after irradiation). We found that a combination of Z-VAD-fmk (50-100 microM) plus necrostatin-1 (20 microM) showed significant radiomitigative effect - from 33.5%-approximately 61.9% in NCCIT cells (treatment at 30 min after the irradiation exposure). No significant protection was afforded by either of these compounds alone. Our results suggest that necroptosis inhibitors - along with other therapeutic modalities - may be promising as mitigators against late radiation-induced cell death. [Description provided by NIOSH]
• Subjects:
  Cytology Laboratories Neoplasms Occupational Health Pathology Radiation Radiation Injuries Safety
• Keywords:
  Carcinomas Cell-damage Cell-metabolism Cell-morphology Cellular-function Embryotoxicity Laboratory-animals Molecular-biology Radiation-injury
• ISSN:
  1096-6080
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Abstract or Summary ; Abstract or Summary
• Place as Subject:
  California ; OSHA Region 3 ; OSHA Region 9 ; Pennsylvania
• CIO:
  National Institute for Occupational Safety and Health (NIOSH) ; National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health ; Workplace Safety & Health
• Location:
  North America ; North America
• Volume:
  126
• NIOSHTIC Number:
  nn:20040661
• Citation:
  Toxicologist 2012 Mar; 126(Suppl 1):441
• Federal Fiscal Year:
  2012
• NORA Priority Area:
  Manufacturing ; Manufacturing
• Performing Organization:
  University of Pittsburgh at Pittsburgh
• Peer Reviewed:
  False
• Start Date:
  20050701
• Source Full Name:
  The Toxicologist. Society of Toxicology 51st Annual Meeting and ToxExpo, March 11-15, 2012, San Francisco, California
• Supplement:
  1
• End Date:
  20160630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:1246c4e1132134592e1253c99e68b58dee4fb065a3923f31a207408f87f480240a042d03c6e02d22157852096a88d34330dfa2edf10ef17210173b1c833a1d00
• Download URL:
  https://stacks.cdc.gov/view/cdc/193451/cdc_193451_DS1.pdf
• File Type:
  [PDF - 467.03 KB ]