Response of Vascular Cells to Oxidative Stress

我们研究了血管细胞和组织对氧化应激的反应。研究结果如下：1。巨噬细胞被认为能够氧化低密度脂蛋白（LDL）。低密度脂蛋白的氧化可能伴随着铁离子的还原。我们有证据表明激活的巨噬细胞可以减少铁离子，而静止的巨噬细胞则不能。我们研究了氧化LDL和抗氧化剂维生素C在人动脉平滑肌细胞中的作用。这些细胞对氧化LDL表现出典型的反应，但用维生素C预处理以剂量依赖的方式消除了这种反应。我们已经获得证据表明血红素加氧酶1在动脉粥样硬化区，特别是巨噬细胞中高表达。已克隆出胱氨酸/谷氨酸转运体cDNA。两种蛋白，4F2hc和xCT，构成转运蛋白。xCT是一种具有12个跨膜结构域的新型蛋白。转运体的活性在维持细胞内谷胱甘肽水平和对氧化应激的耐受性方面是重要的。分析了xCT基因的5'-侧翼区域，发现转录因子Nrf2对转录的调控作用。研究了氧化应激对过氧化物还蛋白I的诱导作用，发现其转录调控与胱氨酸转运蛋白xCT相似。

We have investigated the response to oxidative stress in vascular cells and tissues.The results are as follows :1. Macrophages are thought to be able to oxidize low-density lipoprotein (LDL).Oxidation of LDL is probably coupled with reduction of ferric ion. We have obtained evidence showing that activated macrophages can reduce ferric ion though resting macrophages cannot.2. We have examined the effects of oxidized LDL and the antioxidant vitamin C in human arterial smooth muscle cells. These cells exhibit typical response to oxidized LDL but pretreatment with vitamin C abolishes the response in a dosedependent manner.3. We have obtained evidence showing the high expression of heme oxygenase 1 in atherosclerotic region, particularly in macrophages.4. cDNA for cystine/glutamate transporter has been cloned. Two proteins, 4F2hc and xCT, constitute the transporter. xCT is a novel protein with 12 transmembrane domains. The activity of the transporter is important in maintaining intracellular glutathione level and hence in tolerance to oxidative stress. The 5'-flanking region of xCT gene has been analyzed and the regulation of the transcription by the transcription factor Nrf2 has been found.5. Induction of peroxiredoxin I by oxidative stress has been examined and the transcriptional regulation similar to that of cystine transporter protein xCT has been found.