title: Proteomic analysis of the effects of the immunomodulatory mycotoxin deoxynivalenol.
abstract: The mycotoxin deoxynivalenol (DON) contaminates cereals worldwide and is a common contaminant in the Western European diet. At high doses, DON induces acute gastrointestinal toxicity; chronic, low-dose effects in humans are not well described, but immunotoxicity has been reported. In this study, 2-DE was used to identify proteomic changes in human B (RPMI1788) and T (JurkatE6.1) lymphocyte cell lines after exposure to minimally toxic concentrations (up to 500 ng/mL) for 24 h. Proteins which changed their abundance post treatment, by a greater than 1.4-fold change reproducible in three separate experiments consisting of 36 gels in total, are ubiquitin carboxyl-terminal hydrolase isozyme L3, proteasome subunit β type-4 and α type-6, inosine-5'-monophosphate dehydrogenase 2, GMP synthase, microtubule-associated protein RP/EB family member 1 (EB1), RNA polymerases I, II, III subunit ABC1, triosephosphate isomerase and transketolase. Flow cytometry was used to validate changes to protein expression, except for EB1. These findings provide insights as to how low-dose exposure to DON may affect human immune function and may provide mechanism-based biomarkers for DON exposure.
authors.affiliation: Division of Epidemiology, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds, UK. dacostaa@fellows.iarc.fr
authors.forename: André
authors.initials: A
authors.lastname: Nogueira da Costa
authors.forename: Renée S
authors.initials: RS
authors.lastname: Mijal
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Keen
authors.forename: John B C
authors.initials: JB
authors.lastname: Findlay
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Wild
mesh_terms: D015153:Blotting, Western; D002460:Cell Line; D015180:Electrophoresis, Gel, Two-Dimensional; D005434:Flow Cytometry; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D011506:Proteins / Q000032:analysis; D020543:Proteome / Q000737:chemistry / Q000187:drug effects*; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014255:Trichothecenes / Q000494:pharmacology*
chemical_list: D011506:Proteins; D020543:Proteome; D014255:Trichothecenes; C007262:deoxynivalenol