The Ah receptor is not involved in 2,3,7,8-tetrachlorodibenzo-p-dioxin-mediated apoptosis in human leukemic T cell lines
The Ah receptor is not involved in 2,3,7,8-tetrachlorodibenzo-p-dioxin-mediated apoptosis in human leukemic T cell lines
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DOI：
10.1074/jbc.273.31.19853
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发表时间：
1998-07-31
影响因子：
4.8
通讯作者：
Kikuchi, H
中科院分区：
文献类型：
--
作者：
Hossain, A;Tsuchiya, S;Kikuchi, H
2，3，7，8-四氯二苯并对二恶英(TCDD)是一种常见的环境污染物，引起了人们的关注。它的毒性作用包括扰乱免疫、内分泌和生殖系统，损害胎儿发育，致癌，并对啮齿动物致死。在这里，我们报告了TCDD诱导两个培养的人白血病淋巴母细胞T细胞系的凋亡。这种细胞死亡被发现不依赖于芳香烃受体，并被酪氨酸激酶和半胱氨酸酶的抑制剂抑制。经TCDD处理后，这些细胞中与凋亡相关的c-jun氨基末端激酶被迅速激活。在TCDD治疗中，c-jun氨基末端激酶的显性负性突变体可防止细胞死亡。此外，TCDD还可降低模型大鼠脑内Bcl2蛋白水平。这些细胞系。这些发现将有助于理解TCDD介导的免疫毒性的分子机制。
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a common environmental pollutant causing public concern. Its toxic effects include disruption of the immune, endocrine, and reproductive systems, impairment of fetal development, carcinogenicity, and lethality in rodents. Here, we report that TCDD induces apoptosis in two cultured human leukemic lymphoblastic T cell lines. This cell death was found not to be dependent on an aryl hydrocarbon receptor and to be inhibited by the inhibitor of tyrosine kinases and caspases. Apoptosis-linked c-Jun N-terminal kinase is rapidly activated in these cells by the treatment with TCDD. A dominant-negative mutant of c-Jun N-terminal kinase prevented cell death in the treatment with TCDD. Furthermore, TCDD decreases the Bcl-2 protein level in. these cell lines. These findings will help in the understanding of the molecular mechanism underlying TCDD-mediated immunotoxicity.