The Key Involvement of Poly(ADP-ribosyl)ation in Defense Against Toxic Agents: Molecular Biology Studies

Abstract

We observed that exposure of rat lung alveolar type II epithelial cells (RLE-6TN) to JP-8 in vitro induces biochemical and morphological markers of apoptotic cell death such as activation of caspase-3, cleavage of poly(ADP-ribose) polymerase, chromatin condensation, release of cytochrome c from mitochondria, and cleavage of genomic DNA. Generation of reactive oxygen species (ROS) and depletion of intracellular reduced glutathione (GSH) also showed to play important roles in the induction of programmed cell death by JP-8. With the use of macroarray analysis, we further demonstrated that human Jurkat T cells exposed to JP-8 manifested pronounced changes in the expression of genes related to the cellular response to oxidative stress or to apoptosis. In contrast, similar analysis with normal human keratinocytes revealed that exposure to JP-8 induced changes in the expression of genes whose products function in detoxification or regulation of cell growth These findings might be relevant to the relative resistance of keratinocytes to JP-8 toxicity and support the notion that the induction of cell death by JP-8 may be cell type specific.

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Document Details

Document Type
Technical Report
Publication Date
Oct 30, 2004
Accession Number
ADA427637

Entities

People

  • Mark Smulson

Organizations

  • Georgetown University

Tags

DTIC Thesaurus Topics

  • Apoptosis
  • Biochemistry
  • Biology
  • Body Fluids
  • Cell Physiological Processes
  • Cells
  • Chemistry
  • Dna Microarrays
  • Epithelial Cells
  • Free Radicals
  • Lymphocytes
  • Medical Personnel
  • Molecular Biology
  • Neoplasms
  • Oxidative Stress
  • Programmed Cell Death
  • Proteins

Fields of Study

  • Biology

Readers

  • Cellular and Molecular Pathways of Apoptosis.
  • Immunology and Pathology
  • Molecular Genetics