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
Madhumohan, R.K. ; Hendriksen, P.J.M. ; Loveren, H. van; Peijnenburg, A.A.C.M. - \ 2011
Toxicology and Applied Pharmacology 254 (2011). - ISSN 0041-008X - p. 311 - 322.
endoplasmic-reticulum stress - natural-killer-cells - unfolded protein response - organotin compounds - nuclear-factor - kappa-b - bis(tri-n-butyltin)oxide tbto - nonspecific resistance - antioxidant response - rat thymocytes
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 µM 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.
Differential induction of electrophile-responsive element-regulated genes by n-3 and n-6 polyunsaturated fatty acids
Beelen, V.A. van; Aarts, M.G.M. ; Reus, A. ; Mooibroek, H. ; Sijtsma, L. ; Bosch, H.J. ; Rietjens, I.M.C.M. ; Alink, G.M. - \ 2006
FEBS Letters 580 (2006)19. - ISSN 0014-5793 - p. 4587 - 4590.
antioxidant response - fish-oil - dietary - carcinogenesis - mechanisms - protection - oxidation - reductase - pathway - cancer
In this study the n-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid and docosahexaenoic acid appear to be effective inducers of electrophile-responsive element (EpRE) regulated genes, whereas the n-6 PUFA arachidonic acid is not. These n-3 PUFAs need to be oxidized to induce EpRE-regulated gene expression, as the antioxidant vitamin E can partially inhibit the PUFA induced dose-dependent effect. Results were obtained using a reporter gene assay, real-time RT-PCR and enzyme activity assays. The induction of EpRE-regulated phase II genes by n-3 PUFAs may be a major pathway by which n-3 PUFAs, in contrast to n-6 PUFAs, are chemopreventive and anticarcinogenic.