Burdo J R, Antonetti D A, Wolpert E B, Connor J R
Department of Neuroscience, Pennsylvania State College of Medicine, Mail Code H109, 500 University Drive, Hershey, PA 17033, USA.
Neuroscience. 2003;121(4):883-90. doi: 10.1016/s0306-4522(03)00590-6.
For peripheral iron to reach the brain, it must transverse the blood-brain barrier. In order for the brain to obtain iron, transferrin receptors are present in the vascular endothelial cell to facilitate movement of transferrin bound iron into the brain parenchyma. However, a number of significant voids exist in our knowledge about transport of iron into the brain. These gaps in our knowledge are significant not only because iron is an essential neurotrophic factor but also because the system for delivery of iron into the brain is being viewed as an opportunity to circumvent the blood-brain barrier for delivery of neurotoxins to tumors or trophic factors in neurodegenerative diseases. In this study, we have used fluorescein-transferrin-59Fe in a bovine retinal endothelial cell culture system to determine the mechanism of transferrin-iron transport and to test the hypothesis that the iron status of the endothelial cells would influence iron transport. Our results indicated that iron is transported across endothelial cells both bound to and not bound to transferrin. The ratio of non-transferrin-bound iron to transferrin-bound iron transported is dependent upon the iron status of the cells. Blocking acidification of endosomes led to a significant decrease in transport of non-transferrin-bound iron but not transferrin-bound iron. Blocking pinocytosis had no effect on either transferrin or iron transcytosis. These results indicate that there is both transferrin-mediated and non-transferrin-mediated transcytosis of iron and that the process is influenced by the iron status of the cells. These data have considerable implications for common neurodegenerative diseases that are associated with excess brain iron accumulation and the numerous neurological complications associated with brain iron deficiency.
外周铁要进入大脑，必须穿过血脑屏障。为使大脑获取铁，血管内皮细胞中存在转铁蛋白受体，以促进与转铁蛋白结合的铁进入脑实质。然而，在铁进入大脑的运输方面，我们的知识存在一些重大空白。这些知识空白很重要，不仅因为铁是一种必需的神经营养因子，还因为将铁输送到大脑的系统被视为绕过血脑屏障向肿瘤输送神经毒素或向神经退行性疾病输送营养因子的一个机会。在本研究中，我们在牛视网膜内皮细胞培养系统中使用荧光素 - 转铁蛋白 - 59Fe来确定转铁蛋白 - 铁运输的机制，并检验内皮细胞的铁状态会影响铁运输这一假设。我们的结果表明，铁以与转铁蛋白结合和未结合的形式穿过内皮细胞。运输的非转铁蛋白结合铁与转铁蛋白结合铁的比例取决于细胞的铁状态。阻断内体的酸化会导致非转铁蛋白结合铁的运输显著减少，但不会影响转铁蛋白结合铁的运输。阻断胞饮作用对转铁蛋白或铁的转胞吞作用均无影响。这些结果表明，铁存在转铁蛋白介导和非转铁蛋白介导的转胞吞作用，且该过程受细胞铁状态的影响。这些数据对于与脑铁过量积累相关的常见神经退行性疾病以及与脑铁缺乏相关的众多神经并发症具有重要意义。
