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Title: Exposure of Jurkat cells to bis (tri-n-butyltin) oxide (TBTO) induces transcriptomics changes indicative for ER- and oxidative stress, T cell activation and apoptosis

Abstract

Tributyltin oxide (TBTO) is an organotin compound that is widely used as a biocide in agriculture and as an antifouling agent in paints. TBTO is toxic for many cell types, particularly immune cells. The present study aimed to identify the effects of TBTO on the human T lymphocyte cell line Jurkat. Cells were treated with 0.2 and 0.5 {mu}M TBTO for 3, 6, 12 and 24 h and then subjected to whole genome gene expression microarray analysis. The biological interpretation of the gene expression profiles revealed that endoplasmic reticulum (ER) stress is among the earliest effects of TBTO. Simultaneously or shortly thereafter, oxidative stress, activation of NFKB and NFAT, T cell activation, and apoptosis are induced. The effects of TBTO on genes involved in ER stress, NFAT pathway, T cell activation and apoptosis were confirmed by qRT-PCR. Activation and nuclear translocation of NFATC1 and the oxidative stress response proteins NRF2 and KEAP1 were confirmed by immunocytology. Taking advantage of previously published microarray data, we demonstrated that the induction of ER stress, oxidative stress, T cell activation and apoptosis by TBTO is not unique for Jurkat cells but does also occur in mouse thymocytes both ex vivo and in vivo andmore » rat thymocytes ex vivo. We propose that the induction of ER stress leading to a T cell activation response is a major factor in the higher sensitivity of immune cells above other types of cells for TBTO. - Research Highlights: > The human T lymphocyte cell line Jurkat was exposed to TBTO. > Whole-genome microarray experiments were performed. > Data analysis revealed the induction of ER stress and activation of NFAT and NFKB. > Exposure to TBTO also led to T cell activation, oxidative stress and apoptosis.« less

Authors:
 [1];  [2];  [2];  [1];  [2];  [3];  [4];  [2];  [1];  [2]
  1. RIKILT-Institute of Food Safety, Wageningen University and Research Centre, Wageningen (Netherlands)
  2. (Netherlands)
  3. Department of Health Risk Analysis and Toxicology, Maastricht University (Netherlands)
  4. (RIVM), Bilthoven (Netherlands)
Publication Date:
OSTI Identifier:
21587807
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 254; Journal Issue: 3; Other Information: DOI: 10.1016/j.taap.2011.04.021; PII: S0041-008X(11)00176-1; Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; ENDOPLASMIC RETICULUM; GENES; IN VIVO; LYMPHOCYTES; MICE; ORGANOMETALLIC COMPOUNDS; OXIDATION; OXIDES; POLYMERASE CHAIN REACTION; RATS; STRESSES; THYMOCYTES; TIN COMPOUNDS; ANIMAL CELLS; ANIMALS; BIOLOGICAL MATERIALS; BLOOD; BLOOD CELLS; BODY FLUIDS; CELL CONSTITUENTS; CHALCOGENIDES; CHEMICAL REACTIONS; CONNECTIVE TISSUE CELLS; GENE AMPLIFICATION; LEUKOCYTES; MAMMALS; MATERIALS; ORGANIC COMPOUNDS; OXYGEN COMPOUNDS; RODENTS; SOMATIC CELLS; VERTEBRATES

Citation Formats

Katika, Madhumohan R., Department of Health Risk Analysis and Toxicology, Maastricht University, Netherlands Toxicogenomics Centre, Hendriksen, Peter J.M., Netherlands Toxicogenomics Centre, Loveren, Henk van, National Institute for Public Health and the Environment, Netherlands Toxicogenomics Centre, Peijnenburg, Ad, E-mail: ad.peijnenburg@wur.nl, and Netherlands Toxicogenomics Centre. Exposure of Jurkat cells to bis (tri-n-butyltin) oxide (TBTO) induces transcriptomics changes indicative for ER- and oxidative stress, T cell activation and apoptosis. United States: N. p., 2011. Web. doi:10.1016/j.taap.2011.04.021.
Katika, Madhumohan R., Department of Health Risk Analysis and Toxicology, Maastricht University, Netherlands Toxicogenomics Centre, Hendriksen, Peter J.M., Netherlands Toxicogenomics Centre, Loveren, Henk van, National Institute for Public Health and the Environment, Netherlands Toxicogenomics Centre, Peijnenburg, Ad, E-mail: ad.peijnenburg@wur.nl, & Netherlands Toxicogenomics Centre. Exposure of Jurkat cells to bis (tri-n-butyltin) oxide (TBTO) induces transcriptomics changes indicative for ER- and oxidative stress, T cell activation and apoptosis. United States. doi:10.1016/j.taap.2011.04.021.
Katika, Madhumohan R., Department of Health Risk Analysis and Toxicology, Maastricht University, Netherlands Toxicogenomics Centre, Hendriksen, Peter J.M., Netherlands Toxicogenomics Centre, Loveren, Henk van, National Institute for Public Health and the Environment, Netherlands Toxicogenomics Centre, Peijnenburg, Ad, E-mail: ad.peijnenburg@wur.nl, and Netherlands Toxicogenomics Centre. Mon . "Exposure of Jurkat cells to bis (tri-n-butyltin) oxide (TBTO) induces transcriptomics changes indicative for ER- and oxidative stress, T cell activation and apoptosis". United States. doi:10.1016/j.taap.2011.04.021.
@article{osti_21587807,
title = {Exposure of Jurkat cells to bis (tri-n-butyltin) oxide (TBTO) induces transcriptomics changes indicative for ER- and oxidative stress, T cell activation and apoptosis},
author = {Katika, Madhumohan R. and Department of Health Risk Analysis and Toxicology, Maastricht University and Netherlands Toxicogenomics Centre and Hendriksen, Peter J.M. and Netherlands Toxicogenomics Centre and Loveren, Henk van and National Institute for Public Health and the Environment and Netherlands Toxicogenomics Centre and Peijnenburg, Ad, E-mail: ad.peijnenburg@wur.nl and Netherlands Toxicogenomics Centre},
abstractNote = {Tributyltin oxide (TBTO) is an organotin compound that is widely used as a biocide in agriculture and as an antifouling agent in paints. TBTO is toxic for many cell types, particularly immune cells. The present study aimed to identify the effects of TBTO on the human T lymphocyte cell line Jurkat. Cells were treated with 0.2 and 0.5 {mu}M TBTO for 3, 6, 12 and 24 h and then subjected to whole genome gene expression microarray analysis. The biological interpretation of the gene expression profiles revealed that endoplasmic reticulum (ER) stress is among the earliest effects of TBTO. Simultaneously or shortly thereafter, oxidative stress, activation of NFKB and NFAT, T cell activation, and apoptosis are induced. The effects of TBTO on genes involved in ER stress, NFAT pathway, T cell activation and apoptosis were confirmed by qRT-PCR. Activation and nuclear translocation of NFATC1 and the oxidative stress response proteins NRF2 and KEAP1 were confirmed by immunocytology. Taking advantage of previously published microarray data, we demonstrated that the induction of ER stress, oxidative stress, T cell activation and apoptosis by TBTO is not unique for Jurkat cells but does also occur in mouse thymocytes both ex vivo and in vivo and rat thymocytes ex vivo. We propose that the induction of ER stress leading to a T cell activation response is a major factor in the higher sensitivity of immune cells above other types of cells for TBTO. - Research Highlights: > The human T lymphocyte cell line Jurkat was exposed to TBTO. > Whole-genome microarray experiments were performed. > Data analysis revealed the induction of ER stress and activation of NFAT and NFKB. > Exposure to TBTO also led to T cell activation, oxidative stress and apoptosis.},
doi = {10.1016/j.taap.2011.04.021},
journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 3,
volume = 254,
place = {United States},
year = {2011},
month = {8}
}