Multiple basic-leucine zipper proteins regulate induction of the mouse heme oxygenase-1 gene by arsenite
Multiple basic-leucine zipper proteins regulate induction of the mouse heme oxygenase-1 gene by arsenite
复制标题
DOI：
10.1016/s0003-9861(02)00404-6
复制
发表时间：
2002-09-15
影响因子：
3.9
通讯作者：
Alam, J
中科院分区：
文献类型：
--
作者：
Gong, PF;Stewart, D;Alam, J
探讨了砷对骨氧合酶-1（ho-1）基因的激活机制。亚砷酸钠以剂量依赖性方式刺激小鼠肝癌细胞中ho-1启动子/荧光素酶嵌合体的表达突变分析确定了砷响应序列的应力响应元件（StRE），这类似于碱性亮氨酸拉链因子的AP-1超家族的结合位点。在电泳迁移率变动分析中，多达7个特定的StRE-蛋白复合物常规检测使用未经处理的Hepa细胞的提取物，而一个单一的复合物通常观察到亚砷酸盐处理后。抗体“超移位”实验确定了对照复合物中的Nrf 2、JunD和ATF 3，并且这些因子的量在亚砷酸盐诱导的复合物中显著增加。MafG，ATF 2。FosB和JunB也在亚砷酸盐络合物中被检测到。由亚砷酸盐激活的StRE依赖的荧光素酶基因被抑制到不同程度的显性负突变体Nrf 2，MafK，c-Fos，和CREB，但最强烈的是后者。总之，这些结果暗示多个碱性亮氨酸拉链转录因子在砷激活ho-1基因。(C)2002 Elsevier Science（美国）。All rights reserved.
The mechanism of hone oxygenase-1 (ho-1) gene activation by arsenite was examined. Arsenite-stimulated expression of a ho-1 promoter/luciferase chimera in a dose-dependent manner in mouse hepatoma (Hepa) cells. Mutation analyses identified the arsenite-responsive sequence as the stress-response element (StRE), which resembles the binding sites for the AP-1 superfamily of basic-leucine zipper factors. In electrophoretic mobility shift assays, up to seven specific StRE-protein complexes were routinely detected using extracts from untreated Hepa cells whereas a single complex was typically observed after treatment with arsenite. Antibody "supershift" experiments identified Nrf2, JunD, and ATF3 in control complexes and the amount of these factors increased significantly in the arsenite-induced complex. MafG, ATF2. FosB, and JunB were also detected in the arsenite complex. Activation of a StRE-dependent luciferase gene by arsenite was inhibited to varying degrees by dominant-negative mutants of Nrf2, MafK, c-Fos, and CREB but most strongly with the latter. Together, these results implicate multiple basic-leucine zipper transcription factors in ho-1 gene activation by arsenite. (C) 2002 Elsevier Science (USA). All rights reserved.