Protein expression profiling of mouse thymoma cells upon exposure to the trichothecene deoxynivalenol (DON): implications for its mechanism of action.
The objective of this work was to investigate whether proteomic analysis of thymoma cells treated with the trichothecene deoxynivalenol (DON) as compared to non-treated (control) cells would reveal differential protein expression, and thus would contribute to a better understanding of the mechanisms of its toxicity. For that purpose the mouse thymoma cell line EL4 was exposed to 0.5 microM DON for 6 hr. A total of 30 proteins were affected after exposure of EL4 cells to DON. Most of these proteins were up-regulated and included key metabolic enzymes (e.g., fatty acid synthase, aldose reductase, carbamoyl phosphate synthetase, glucose-6-phosphate isomerase), chaperones (e.g., HSP9AB1 and HSP70), enzymes implicated in protein folding (PDI and ERO1-l alpha), and proteins involved in protein degradation (ubiquitin-conjugating enzyme (E1) and proteasome subunit alpha type-1). In addition, an IgE-binding protein with a molecular weight of 60 kDa and My-binding protein 1a (MYBBP1A), a transcription factor, were found to be up-regulated by DON. The observed up-regulation of MYBBP1A, a known repressor of a number of transcription factors such as PGC-1 alpha, C-myb, and p65 of the NF-kappaB family, suggests that this protein might play a role in the mechanism of DON toxicity.
Osman
Ahmed M
AM
National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. Ahmed.Osman@rivm.nl
Pennings
Jeroen L A
JL
Blokland
Marco
M
Peijnenburg
Ad
A
van Loveren
Henk
H
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins; D020869:Gene Expression Profiling; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000235:genetics / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D017510:Protein Folding / Q000187:drug effects; D040901:Proteomics / Q000379:methods; D016601:RNA-Binding Proteins; D013945:Thymoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors; D014255:Trichothecenes / Q000633:toxicity*; D015854:Up-Regulation
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C110421:Mybbp1a protein, mouse; D016328:NF-kappa B; D009687:Nuclear Proteins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D016601:RNA-Binding Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D014255:Trichothecenes; D010447:Peptide Hydrolases; D046988:Proteasome Endopeptidase Complex; C007262:deoxynivalenol