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
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
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DOI：
10.1016/j.taap.2011.04.021
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发表时间：
2011-08-01
影响因子：
3.8
通讯作者：
Peijnenburg, Ad
中科院分区：
文献类型：
--
作者：
Katika, Madhumohan R.;Hendriksen, Peter J. M.;Peijnenburg, Ad
三丁基氧化锡 (TBTO) 是一种有机锡化合物，广泛用作农业中的杀菌剂和油漆中的防污剂。 TBTO 对许多细胞类型有毒，尤其是免疫细胞。本研究旨在确定 TBTO 对人 T 淋巴细胞系 Jurkat 的影响。用0.2和0.5μM TBTO处理细胞3、6、12和24小时，然后进行全基因组基因表达微阵列分析。基因表达谱的生物学解释表明，内质网 (ER) 应激是 TBTO 最早的影响之一。同时或此后不久，氧化应激、NFKB 和 NFAT 激活、T 细胞激活和细胞凋亡被诱导。 qRT-PCR 证实了 TBTO 对 ER 应激、NFAT 通路、T 细胞活化和凋亡相关基因的影响。通过免疫细胞学证实了 NFATC1 以及氧化应激反应蛋白 NRF2 和 KEAP1 的激活和核转位。利用之前发表的微阵列数据，我们证明TBTO诱导内质网应激、氧化应激、T细胞活化和凋亡并不是Jurkat细胞所独有的，而且也发生在离体和体内的小鼠胸腺细胞以及离体的大鼠胸腺细胞中。我们认为，诱导 ER 应激导致 T 细胞激活反应是免疫细胞对 TBTO 的敏感性高于其他类型细胞的主要因素。 (C) 2011 Elsevier Inc. 保留所有权利。
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. (C) 2011 Elsevier Inc. All rights reserved.