Cellular management of iron in the brain
Cellular management of iron in the brain
复制标题
DOI：
10.1016/0022-510x(95)00206-h
复制
发表时间：
1995-12-01
影响因子：
4.4
通讯作者：
Menzies, SL
中科院分区：
文献类型：
--
作者：
Connor, JR;Menzies, SL
包括大脑在内的所有器官都含有铁以及参与铁吸收的蛋白质（转铁蛋白和转铁蛋白受体）和细胞内储存（铁蛋白）。然而，由于大脑位于屏障后面，并且具有异质细胞群，因此其铁管理的某些方面是独特的。铁管理，及时提供适量的铁，对正常的大脑发育和功能至关重要。细胞铁的管理不当不仅会导致代谢活性降低，而且会增加对氧化损伤的脆弱性。细胞铁沉积和铁调节蛋白具有区域特异性。然而，铁在大脑中的螯合似乎主要是少突胶质细胞的责任，因为这些细胞含有大脑中大部分的铁。铁动员蛋白转铁蛋白也主要存在于这些细胞中。转铁蛋白受体在血管、皮质、纹状体和海马中的大神经元上大量表达，并且也存在于少突胶质细胞和星形胶质细胞上。铁蛋白，细胞内的铁储存蛋白，由2个功能不同的亚基组成，我们在这份报告中提供的证据表明，铁蛋白亚基的细胞分布也是不同的。此外，铁及其相关调节蛋白的细胞分布的变化发生在阿尔茨海默病中。神经炎斑含有相对大量的铁，周围细胞对铁蛋白和转铁蛋白受体有强烈的免疫染色。铁的细胞分布的分析表明，不同类型的细胞对铁的需求水平不同，最终应该阐明细胞如何获得和维持氧化代谢的这一重要组成部分。此外，细胞输送和管理铁的能力的变化可以深入了解随着年龄和疾病而改变的代谢活动，并识别面临铁诱导的氧化应激风险的细胞群。
All organs including the brain contain iron, and the proteins involved in iron uptake (transferrin and transferrin receptor) and intracellular storage (ferritin). However, because the brain resides behind a barrier and has a heterogeneous population of cells, there are aspects of its iron management that are unique. Iron management, the timely delivery of appropriate amounts of iron, is crucial to normal brain development and function. Mismanagement of cellular iron can result not only in decreased metabolic activity but increased vulnerability to oxidative damage. There is regional specificity in cell deposition of iron and the iron regulatory proteins. However, the sequestration of iron in the brain seems primarily the responsibility of oligodendrocytes, as these cells contain most of the stainable iron in the brain. Transferrin, the iron-mobilizing protein, is also found predominantly in these cells. The transferrin receptor is abundantly expressed on blood vessels, large neurons in the cortex, striatum, and hippocampus, and is also present on oligodendrocytes and astrocytes. Ferritin, the intracellular iron storage protein, consists of 2 subunits which are functionally distinct, and we provide evidence in this report that the cellular distribution of the ferritin subunits is also distinct. In addition, changes in the cellular distribution of iron and its associated regulatory proteins occur in Alzheimer's disease. Neuritic plaques contain relatively large amounts of stainable iron, and the surrounding cells robustly immunostain for ferritin and the transferrin receptor. Analysis of the cellular distribution of iron indicates the different levels of requirement of iron in the brain by different cell types and should ultimately elucidate how cells acquire and maintain this essential component of oxidative metabolism. In addition, changes in the ability of cells to deliver and manage iron may provide insight into altered metabolic activity with age and disease as well as identify cell populations at risk for iron-induced oxidative stress.