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.

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Record number 427044
Title Immunocytological and biochemical analysis of the mode of action of bis (tri-n-butyltin) tri-oxide (TBTO) in Jurkat cells
Author(s) Katika, M.R.; Hendriksen, P.J.M.; Ruijter, N.C.A. de; Loveren, H. van; Peijnenburg, A.A.C.M.
Source Toxicology Letters 212 (2012)2. - ISSN 0378-4274 - p. 126 - 136.
DOI https://doi.org/10.1016/j.toxlet.2012.05.010
Department(s) Rikilt B&T Toxicologie en Effectanalyse
Laboratory of Cell Biology
RIKILT - Business Unit Safety & Health
Publication type Refereed Article in a scientific journal
Publication year 2012
Keyword(s) natural-killer-cells - environmentally relevant concentrations - endoplasmic-reticulum stress - cytochrome-c release - induced apoptosis - er stress - bis(tri-n-butyltin)oxide tbto - oxidative stress - t-cell - immunohistochemical expression
Abstract Bis (tri-n-butyltin) oxide (TBTO) is one of the organotin compounds known to induce immunosuppression. Previously, we examined the effect of TBTO on whole-genome mRNA expression in the human T lymphocyte cell line Jurkat, which led to the hypothesis that induction of endoplasmic reticulum (ER) stress is the first initiated event, which induces a rise of intracellular calcium levels, activation of NF-kB and NFAT, T cell activation response and oxidative stress together finally resulting in apoptosis. The present study verified this hypothesis with biochemical and cytological experiments. The induction of ER stress was confirmed by the rapid raise in protein levels of ATF3 and DDIT3. Moreover, the impairment of cell viability by TBTO was moderated by the ER stress inhibitor phenyl butyric acid. Real-time fluorescence microscopy confirmed that TBTO increases intracellular calcium levels within 2min of exposure. Furthermore, the involvement of increased calcium levels in the effects of TBTO was evident from the induction of three calcium-dependent events: (1) activation of the protease activity of M-calpain, (2) induction of NF-kB (p65) expression, and (3) activation of NFAT. The induction of oxidative stress was verified by detection of increased levels of reactive oxygen species and a decrease in amount of reduced glutathione. We also showed that TBTO induces cleavage of caspase-3, an event known to mediate apoptosis. Finally, comparative microarray data analysis showed that many of the processes observed in vitro also occur in vivo in thymuses of TBTO-treated mice.
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