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Published on: October 1, 2012
Proteomics study of anthrax lethal toxin-treated murine macrophages
Jeffrey F Kuhn1, Patric Hoerth, Silvia T Hoehn
1National Institute of Environmental Health Sciences, NIH/DHHS, Research Triangle Park, NC 27709, USA. kuhn1@niehs.nih.gov
Electrophoresis
|April 13, 2006
Summary
Anthrax lethal toxin (LeTx) triggers cell death by targeting the MAP kinase pathway. Proteomics identified 67 proteins involved in oxidative stress and apoptosis, revealing a compromised tumor necrosis factor-alpha pathway in intoxicated cells.
Area of Science:
- Cellular Biology
- Proteomics
- Toxicology
Background:
- Anthrax lethal toxin (LeTx) comprises protective antigen and lethal factor.
- LeTx enters cells via the anthrax toxin receptor (ATR).
- LeTx targets p38 within the MAP kinase signaling pathway, initiating apoptosis.
Purpose of the Study:
- To investigate downstream targets of LeTx.
- To identify cellular processes affected by LeTx.
- To understand the molecular mechanisms of anthrax pathogenesis.
Main Methods:
- Proteomics approach utilizing improved isoelectric focusing (pI) fractionation.
- Off-gel electrophoresis for protein separation.
- Mass labeling for relative protein quantitation in RAW 264.7 cell cytosol.
Main Results:
- Quantified 67 proteins differentially expressed in toxin-treated versus control cells.
- Identified proteins involved in oxidative stress response and apoptosis.
- Observed a compromised tumor necrosis factor-alpha-mediated pathway.
Conclusions:
- LeTx affects multiple cellular pathways, including oxidative stress and apoptosis.
- The tumor necrosis factor-alpha pathway is significantly impacted by LeTx.
- Understanding these molecular changes is crucial for developing strategies against anthrax.
