期刊
PROGRESS IN NEUROBIOLOGY
卷 186, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pneurobio.2019.101744
关键词
Iron; Ferroprotein; Aging; Inductively coupled plasma-mass spectrometry
资金
- National Health AMP
- Medical Research Council
- Australian Research Council
- NHMRC-ARC Dementia Research Development Fellowship [GNT1105791]
- NHMRC Career Development Fellowship - Industry [GNT1122981]
- Agilent Technologies Australia
- NHMRC [GNT 1103703, GNT1138673, GNT1164692]
- ARC [DP180101248, LP14010095]
- Agilent Technologies
- Victorian Government
- Operational Infrastructure Support Grant
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.
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