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毒死蜱可诱导人T细胞凋亡。

Chlorpyrifos induces apoptosis in human T cells.

作者信息

Li Qing, Kobayashi Maiko, Kawada Tomoyuki

机构信息

Department of Hygiene and Public Health, Nippon Medical School, 1-1-5 Sendagi, 113-8602 Tokyo, Japan.

出版信息

Toxicology. 2009 Jan 8;255(1-2):53-7. doi: 10.1016/j.tox.2008.10.003. Epub 2008 Oct 17.

Abstract

It was found previously that organophosphorus pesticides (OPs) significantly inhibited cytotoxic T lymphocyte (CTL) activity. To explore the mechanism of OP-induced inhibition of CTL activity, the present study investigated whether OPs can induce cell death/apoptosis in T cells. Jurkat human T cells were treated with chlorpyrifos at 0-100 ppm for 2, 4, and 6h at 37 degrees C in vitro. It was found that chlorpyrifos induced cell death of Jurkat human T cells in a dose- and time-dependent manner, as shown by MTT and LDH assays. Then, it was investigated if chlorpyrifos-induced cell death consisted of apoptosis, as determined by analysis of Annexin-V staining and the intracellular level of active caspase-3 by flow cytometry, and DNA fragmentation analysis. It was found that chlorpyrifos induces apoptosis in Jurkat T cells in a dose- and time-dependent manner, as determined by analysis of Annexin-V staining. DNA fragmentation was detected when cells were treated with 50 or 100 ppm chlorpyrifos for 4 and 6h. Chlorpyrifos also induced an increase in intracellular active caspase-3 in Jurkat T cells in a dose- and time-dependent manner, and a caspase-3 inhibitor, Z-DEVD-FMK, significantly inhibited chlorpyrifos-induced apoptosis. These findings indicate that chlorpyrifos can induce apoptosis in human Jurkat T cell cells, and this effect is partially mediated by the activation of intracellular caspase-3.

摘要

先前发现有机磷农药(OPs)能显著抑制细胞毒性T淋巴细胞(CTL)的活性。为探究OPs抑制CTL活性的机制,本研究调查了OPs是否能诱导T细胞发生细胞死亡/凋亡。将Jurkat人T细胞在37℃下用0 - 100 ppm的毒死蜱体外处理2、4和6小时。如MTT和LDH检测所示,发现毒死蜱以剂量和时间依赖性方式诱导Jurkat人T细胞死亡。然后,通过流式细胞术分析膜联蛋白V染色和细胞内活性半胱天冬酶 - 3水平以及DNA片段化分析,研究毒死蜱诱导的细胞死亡是否由凋亡组成。通过膜联蛋白V染色分析确定,发现毒死蜱以剂量和时间依赖性方式诱导Jurkat T细胞凋亡。当细胞用50或100 ppm毒死蜱处理4和6小时时,检测到DNA片段化。毒死蜱还以剂量和时间依赖性方式诱导Jurkat T细胞内活性半胱天冬酶 - 3增加,并且半胱天冬酶 - 3抑制剂Z - DEVD - FMK显著抑制毒死蜱诱导的凋亡。这些发现表明毒死蜱可诱导人Jurkat T细胞凋亡,且这种作用部分由细胞内半胱天冬酶 - 3的激活介导。

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