Transcriptional profiling of whole blood and serum protein analysis of mice exposed to the neurotoxin Pacific Ciguatoxin-1

Neurotoxicology. 2007 Nov;28(6):1099-109. doi: 10.1016/j.neuro.2007.05.013. Epub 2007 Jun 16.

Abstract

Ciguatoxins (CTX) are a suite of cyclic polyether toxins produced by the marine dinoflagellate Gambierdiscus sp., are potent activators of voltage-gated sodium channels and a leading cause of human poisoning from food fish. This report characterizes the genomic and proteomic response in whole blood of adult male mice exposed i.p. to 264 ng/kg of the Pacific congener of CTX (P-CTX-1) at 1, 4 and 24h. Whole genome microarray expression data were filtered by tightness of fit between replicates, fold change (1.8) and p-value (10(-5)), resulting in 183 annotated genes used for trending analysis, K-means clustering and ontology classification. Genes involved with cytokine signaling, proteasome complex and ribosomal function were dominant. qPCR performed on 19 genes of interest had a correlation of 0.95 to array results by Pearson's correlation coefficient. Serum protein analysis showed small but significant changes in 6 of 60 proteins assayed: Ccl2, Ccl12, CD40, IL-10, leptin and M-CSF. In large part, the gene expression was consistent with a Th2 immune response with interesting similarities to expression seen in asthmatic models.

MeSH terms

  • Animals
  • Antibody Formation / genetics
  • Blood Proteins / metabolism*
  • Ciguatera Poisoning / blood*
  • Ciguatera Poisoning / genetics
  • Ciguatera Poisoning / immunology
  • Ciguatoxins
  • Cluster Analysis
  • Disease Models, Animal
  • Gene Expression Profiling* / methods
  • Immunoassay
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Oligonucleotide Array Sequence Analysis
  • Proteomics* / methods
  • RNA / blood*
  • Reproducibility of Results
  • Reverse Transcriptase Polymerase Chain Reaction
  • Th2 Cells / immunology
  • Time Factors
  • Transcription, Genetic / drug effects*

Substances

  • Blood Proteins
  • Ciguatoxins
  • RNA