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Regional iron distribution and soluble ferroprotein profiles in the healthy human brain.
Progress in Neurobiology ( IF 6.7 ) Pub Date : 2019-12-20 , DOI: 10.1016/j.pneurobio.2019.101744
Erin J McAllum 1 , Dominic J Hare 1 , Irene Volitakis 1 , Catriona A McLean 2 , Ashley I Bush 1 , David I Finkelstein 3 , Blaine R Roberts 3
Affiliation  

Iron is essential for brain development and health where its redox properties are used for a number of neurological processes. However, iron is also a major driver of oxidative stress if not properly controlled. Brain iron distribution is highly compartmentalised and regulated by a number of proteins and small biomolecules. Here, we examine heterogeneity in regional iron levels in 10 anatomical structures from seven post-mortem human brains with no apparent neuropathology. Putamen contained the highest levels, and most case-to-case variability, of iron compared with the other regions examined. Partitioning of iron between cytosolic and membrane-bound iron was generally consistent in each region, with a slightly higher proportion (55 %) in the 'insoluble' phase. We expand on this using the Allen Human Brain Atlas to examine patterns between iron levels and transcriptomic expression of iron regulatory proteins and using quantitative size exclusion chromatography-inductively coupled plasma-mass spectrometry to assess regional differences in the molecular masses to which cytosolic iron predominantly binds. Approximately 60 % was associated with ferritin, equating to approximately 25 % of total tissue iron essentially in storage. This study is the first of its kind in human brain tissue, providing a valuable resource and new insight for iron biologists and neuroscientists, alike.

中文翻译:

健康人脑中的区域铁分布和可溶性铁蛋白谱。

铁是大脑发育和健康必不可少的元素,其氧化还原特性可用于许多神经系统过程。但是,如果控制不当,铁也是氧化应激的主要驱动力。脑铁的分布高度分隔,并受多种蛋白质和小生物分子的调节。在这里,我们检查了来自七个死后人类大脑的10个解剖结构中区域铁水平的异质性,没有明显的神经病理学。与所检查的其他区域相比,果壳中铁含量最高,且随情况变化最大。铁在胞质和膜结合铁之间的分配在每个区域通常是一致的,在“不溶”相中比例较高(55%)。我们使用艾伦人脑图集对此进行扩展,以检查铁水平和铁调节蛋白的转录组表达之间的模式,并使用定量尺寸排阻色谱-电感耦合等离子体质谱法评估胞质铁主要结合的分子质量的区域差异。 。大约60%与铁蛋白相关,基本上等于存储中总组织铁的25%。这项研究是人类脑组织中的首次此类研究,为铁生物学家和神经科学家提供了宝贵的资源和新见解。
更新日期:2019-12-20
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