Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Record number 478370
Title DON shares a similar mode of action as the ribotoxic stress inducer anisomycin while TBTO shares ER stress patterns with the ER stress inducer Thapsigargin based on comparative gene expression profiling in Jurkat T cells
Author(s) Schmeits, P.C.J.; Katika, M.R.; Peijnenburg, A.A.C.M.; Loveren, H. van; Hendriksen, P.J.M.
Source Toxicology Letters 224 (2014)3. - ISSN 0378-4274 - p. 395 - 406.
DOI https://doi.org/10.1016/j.toxlet.2013.11.005
Department(s) RIKILT - BU Toxicology Bioassays & Novel Foods
Publication type Refereed Article in a scientific journal
Publication year 2014
Keyword(s) tri-n-butyltin - unfolded protein response - tributyltin-oxide tbto - mouse thymoma cells - deoxynivalenol don - induced apoptosis - plasma-membrane - ribosomal-rna - in-vivo - activation
Abstract Previously, we studied the effects of deoxynivalenol (DON) and tributyltin oxide (TBTO) on whole genome mRNA expression profiles of human T lymphocyte Jurkat cells. These studies indicated that DON induces ribotoxic stress and both DON and TBTO induced ER stress which resulted into T-cell activation and apoptosis. The first goal of the present study was to provide final proof for these mode of actions by comparing the effects of 6 h exposure to DON and TBTO on mRNA expression to those of positive controls of ribotoxic stress (anisomycin), ER stress (thapsigargin) and T cell activation (ionomycin). Genes affected by anisomycin and the majority of genes affected by thapsigargin were affected in the same direction by DON and TBTO, respectively, confirming the expected modes of action. Pathway analysis further sustained that DON induces ribotoxic stress and both DON and TBTO induce unfolded protein response (UPR), ER stress, T cell activation and apoptosis. The second goal was to assess whether DON and/or TBTO affect other pathways above those detected before. TBTO induced groups of genes that are involved in DNA packaging and heat shock response that were not affected by thapsigargin. DON did not affect other genes than anisomycin indicating the effect of DON to be restricted to ribotoxic stress. This study also demonstrates that comparative gene expression analysis is a very promising tool for the identification of modes of action of immunotoxic compounds.
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