An analysis of the phosphoproteome of immune cell lines exposed to the immunomodulatory mycotoxin deoxynivalenol

Biochim Biophys Acta. 2011 Jul;1814(7):850-7. doi: 10.1016/j.bbapap.2011.04.001. Epub 2011 Apr 13.

Abstract

The mycotoxin deoxynivalenol (DON) commonly contaminates cereal grains. It is ubiquitous in the Western European diet, although chronic, low-dose effects in humans are not well described, but immunotoxicity has been reported. In this study, two-dimensional gel electrophoresis was used to identify phosphoproteomic changes in human B (RPMI1788) and T (Jurkat E6.1) lymphocyte cell lines after exposure to modest concentrations of DON (up to 500ng/mL) for 24h. Proteins identified as having altered phosphorylation state post-treatment (C-1-tetrahydrofolate synthase, eukaryotic elongation factor 2, nucleoside diphosphate kinase A, heat shock cognate 71kDa protein, eukaryotic translation initiation factor 3 subunit I and growth factor receptor-bound protein 2) are involved in regulation of metabolic pathways, protein biosynthesis and signaling transduction. All exhibited a greater than 1.4-fold change, reproducible in three separate experiments consisting of 36 gels in total. Flow cytometry validated the observations for eukaryotic elongation factor 2 and growth factor receptor-bound protein 2. These findings provide further insights as to how low dose exposure to DON may affect human immune function and may have potential as mechanism-based phosphoprotein biomarkers for DON exposure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Lymphocytes / drug effects
  • B-Lymphocytes / metabolism
  • Cell Line
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Electrophoresis, Gel, Two-Dimensional
  • Flow Cytometry
  • Humans
  • Lymphocytes / drug effects*
  • Lymphocytes / metabolism
  • Mycotoxins / pharmacology
  • Phosphoproteins / analysis*
  • Phosphorylation / drug effects
  • Proteome / analysis*
  • Proteome / metabolism
  • Proteomics / methods*
  • Reproducibility of Results
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / metabolism
  • Time Factors
  • Trichothecenes / pharmacology*

Substances

  • Mycotoxins
  • Phosphoproteins
  • Proteome
  • Trichothecenes
  • deoxynivalenol