Characterization and Modulation of Proteins Involved in Sulfur Mustard Vesication

Abstract

Sulfur Mustard(SM) causes death and detachment of the basal cells of the epidermis, and thus is a strong vesicating agent. To design a therapeutic strategy, we have examined the role of apoptosis in SM vesication. We found that SM induces differentiation and apoptosis in human keratinocytes. Furthermore, apoptosis occurs via both a calmodulin- dependent mitochondrial pathway as well as by a FADD-dependent death receptor pathway. In the last year, we found antiapoptotic members of the Bcl-2 family are down-regulated and the proapoptotic member, Bax, is upregulated. In addition, Bad is dephosphorylated, leading to mitochondrial pathways of apoptosis. These events were inhibited by CaM antisense or CaM chemical inhibitors. Finally, we designed a FADD-DN vector which also inhibits the death receptor pathway of SM-induced kertinocyte apoptosis. The CaM-Bcl-2 and Fas-FADD pathways therefore represent attractive targets for therapeutic intervention.

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Document Details

Document Type
Technical Report
Publication Date
May 01, 2002
Accession Number
ADA407323

Entities

People

  • Dean S. Rosenthal

Organizations

  • Georgetown University

Tags

DTIC Thesaurus Topics

  • Apoptosis
  • Biological Factors
  • Biomedical Research
  • Cell Membrane
  • Cell Physiological Processes
  • Cells
  • Chemistry
  • Epithelial Cells
  • Inhibitors
  • Intracellular Membranes
  • Materials
  • Medical Personnel
  • Modulation
  • Molecular Biology
  • Neoplasms
  • Programmed Cell Death
  • Proteins

Fields of Study

  • Biology

Readers

  • Cellular and Molecular Pathways of Apoptosis.
  • Geochemistry