Transcriptional profiling of whole blood and serum protein analysis of mice exposed to the neurotoxin Pacific Ciguatoxin-1.
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.
Ryan
James C
JC
Marine Biotoxins Program, NOAA Center for Coastal Environmental Health and Biomolecular Research, Charleston, SC 29412, United States. james.ryan@noaa.gov
Bottein Dechraoui
Marie-Yasmine
MY
Morey
Jeanine S
JS
Rezvani
Amir
A
Levin
Edward D
ED
Gordon
Christopher J
CJ
Ramsdell
John S
JS
Van Dolah
Frances M
FM
D000818:Animals; D000917:Antibody Formation / Q000235:genetics; D001798:Blood Proteins / Q000378:metabolism*; D036841:Ciguatera Poisoning / Q000097:blood* / Q000235:genetics / Q000276:immunology; D002922:Ciguatoxins; D016000:Cluster Analysis; D004195:Disease Models, Animal; D020869:Gene Expression Profiling / Q000379:methods; D007118:Immunoassay; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D040901:Proteomics / Q000379:methods; D012313:RNA / Q000097:blood*; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018418:Th2 Cells / Q000276:immunology; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects*
D001798:Blood Proteins; D002922:Ciguatoxins; D012313:RNA