Identifying candidate serum biomarkers of exposure to tunicamycins in rats using two-dimensional electrophoresis

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dc.contributor.authorPenno, M.
dc.contributor.authorBacic, A.
dc.contributor.authorColegate, S.
dc.contributor.authorHoffmann, P.
dc.contributor.authorMichalski, W.
dc.date.issued2009
dc.descriptionCopyright © 2009 American Chemical Society
dc.description.abstractA model for chronic corynetoxins poisoning has been established in rats exposed to the toxicologically bioequivalent inhibitor of N-linked glycosylation the tunicamycins. Consumption of corynetoxins in contaminated pasture can result in the often fatal neurological disease of grazing livestock annual ryegrass toxicity (ARGT). Corynetoxins may also threaten human health as potential contaminants of the food supply via grain or products derived from subclinically exposed animals. The serum proteomes of four dose groups plus a control group following 6, 9, and 12 months dietary tunicamycins exposure were compared by one-dimensional electrophoresis. Numerous differences were observed between the control and the highest dose group (40.5 mug tunicamycins/kg of body weight/day), designated as High). Accordingly, these samples were further examined using two-dimensional electrophoresis. Thirty-three protein spots were found to be differentially displayed between the Control and High dose sera based on univariate statistics (p < 0.05 for log(10) transformed normalized volumes) and significant fold-changes in spot volume (+/-2.3-fold as determined by posthoc power analysis). Identities for 28 spots were obtained by MALDI-TOF MS corresponding to 13 different proteins. An increasing population of carbohydrate deficient transferrin was identified in the High dose sera using a combination of antibody and lectin detection and confirmed by ESI-IT MS/MS. The functionalities of other identified proteins were consistent with the oxidative stress and acute phase responses. The biomarkers identified in this study may not only play a useful role in diagnosing toxin exposure but could be helpful in identifying new treatment strategies for ARGT and equivalent human diseases.
dc.description.statementofresponsibilityMegan A. S. Penno, Antony Bacic, Steven M. Colegate, Peter Hoffmann and Wojtek P. Michalski
dc.identifier.citationJournal of Proteome Research, 2009; 8(6):2812-2826
dc.identifier.doi10.1021/pr801111a
dc.identifier.issn1535-3893
dc.identifier.issn1535-3907
dc.identifier.orcidPenno, M. [0000-0002-9617-0826]
dc.identifier.urihttp://hdl.handle.net/2440/51476
dc.language.isoen
dc.publisherAmerican Chemical Society
dc.source.urihttps://doi.org/10.1021/pr801111a
dc.subjectAnimals
dc.subjectRats
dc.subjectGlycolipids
dc.subjectBlood Proteins
dc.subjectTransferrin
dc.subjectProteome
dc.subjectTunicamycin
dc.subjectElectrophoresis, Gel, Two-Dimensional
dc.subjectAnalysis of Variance
dc.subjectToxicity Tests, Chronic
dc.subjectAmino Acid Sequence
dc.subjectGlycosylation
dc.subjectMolecular Sequence Data
dc.subjectFemale
dc.subjectMale
dc.subjectTandem Mass Spectrometry
dc.subjectBiomarkers
dc.titleIdentifying candidate serum biomarkers of exposure to tunicamycins in rats using two-dimensional electrophoresis
dc.typeJournal article
pubs.publication-statusPublished

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