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Abstract：
Metallothionein (MT) is a low-molecular-weight, cysteine-rich, and metal-binding protein that protects cells from the cytotoxic effects of heavy metals and reactive oxygen species. Previously, we found that transcriptional induction of endothelial MT-1A was mediated by not only the metal-regulatory transcription factor 1 (MTF-1)-metal responsive element (MRE) pathway but also the nuclear factor-erythroid 2-related factor 2 (Nrf2)-antioxidant response element/electrophile responsive element (ARE) pathway, whereas that of MT-2A was mediated only by the MTF-1-MRE pathway, using the organopnictogen compounds tris(pentafluorophenyl)stibane, tris(pentafluorophenyl)arsane, and tris(pentafluorophenyl)phosphane as molecular probes in vascular endothelial cells. In the present study, we investigated the binding sites of MTF-1 and Nrf2 in the promoter regions of MTs in cultured bovine aortic endothelial cells treated with these organopnictogen compounds. We propose potential mechanisms underlying transcriptional induction of endothelial MT isoforms. Specifically, both MRE activation by MTF-1 and that of ARE in the promoter region of the MT-2A gene by Nrf2 are involved in transcriptional induction of MT-1A, whereas only MRE activation by MTF-1 or other transcriptional factor(s) is required for transcriptional induction of MT-2A in vascular endothelial cells.
摘要：
金属硫蛋白（MT）是一种低分子量，富含半胱氨酸,和保护细胞免受重金属和活性氧的细胞毒性作用的金属结合蛋白。以前,我们发现内皮MT-1A的转录诱导不仅通过金属调节转录因子1（MTF-1）-金属反应元件（MRE）途径介导，而且还通过核因子-红系2相关因子2（Nrf2）-抗氧化反应元件/亲电反应元件（ARE）途径介导，而MT-2A仅由MTF-1-MRE途径介导，使用有机元素化合物三（五氟苯基）stibane，三（五氟苯基）arsane，和三（五氟苯基）磷烷作为血管内皮细胞的分子探针。在本研究中,我们研究了MTF-1和Nrf2在MTs启动子区的结合位点,在用这些有机免疫原化合物处理的培养的牛主动脉内皮细胞中.我们提出了内皮MT亚型转录诱导的潜在机制。具体来说,MTF-1激活的MRE和Nrf2在MT-2A基因启动子区的ARE都参与MT-1A的转录诱导，而在血管内皮细胞中MT-2A的转录诱导仅需要MTF-1或其他转录因子的MRE激活。
