DNA Damage-Induced Apoptosis: Inhibition by Calmodulin Antagonist, Fas Receptor Antibody and Caspase Inhibitors

Abstract

Sulfur mustard (HD, bis-(2-chloroethyl) sulfide) is a vesicant that causes DNA strand breaks and apoptosis in cultured normal human epidermal keratinocytes (NHEK). HD causes apoptosis via two independent pathways, a Ca2+/calmodulin (CaM)-mediated mitochondrial pathway and Fas receptor (CD95) pathway. We studied the effects of the exogenously added CaM antagonist W7, the CD95 antibody, the caspase-3 inhibitor Ac-DEVD-CHO, and the general caspase inhibitor Z-VAD-fmk on NHEK viability loss (Calcein AM fluorescence assay, LDH release assay) due to HD. All protected against HD. Z-VAD-fmk was the most effective. These results provide a logical approach toward developing an anti-apoptotic vesicant countermeasure.

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Document Details

Document Type
Technical Report
Publication Date
Jul 01, 2003
Accession Number
ADA484661

Entities

People

  • B. J. Benton
  • D. R. Anderson
  • D. S. Rosenthal
  • J. P. Petrali
  • K. R. Bhat
  • M. E. Burke
  • Patrick Ray
  • R. Ray
  • T. Rockwood
  • W. J. Smith

Organizations

  • United States Army Medical Research Institute of Chemical Defense

Tags

Communities of Interest

  • Biomedical

DTIC Thesaurus Topics

  • Abstracts
  • Antibodies
  • Apoptosis
  • Biomedical Research
  • Cell Physiological Processes
  • Cell Physiology
  • Cells
  • Fluorescence
  • Information Operations
  • Inhibitors
  • Intervention
  • Medical Countermeasures
  • Programmed Cell Death
  • Proteins
  • Tissue Culture
  • Viability

Fields of Study

  • Biology

Readers

  • Geochemistry
  • Molecular and Cellular Biochemistry
  • Oncology (Cancer Research).