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

Journal Article · Mon Aug 01 00:00:00 EDT 2011 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2011.04.021· OSTI ID:21587807

Katika, Madhumohan R ^[1]; Centre, Netherlands Toxicogenomics ^[2]; Hendriksen, Peter J.M. ^[1]; Centre, Netherlands Toxicogenomics ^[2]; Loveren, Henk van ^[3]; Centre, Netherlands Toxicogenomics ^[2]; Peijnenburg, Ad ^[1]; Centre, Netherlands Toxicogenomics ^[2]

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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)

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.

• OSTI ID: 21587807
• Journal Information: Toxicology and Applied Pharmacology, Vol. 254, 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); ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

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