Localization of copper and copper transporters in the human brain.
Disturbances in brain copper result in rare and severe neurological disorders and may play a role in the pathogenesis and progression of multiple neurodegenerative diseases. Our current understanding of mammalian brain copper transport is based on model systems outside the central nervous system and no data are available regarding copper transport systems in the human brain. To address this deficit, we quantified regional copper concentrations and examined the distribution and cellular localization of the copper transport proteins Copper transporter 1, Atox1, ATP7A, and ATP7B in multiple regions of the human brain using inductively coupled plasma-mass spectrometry, Western blot and immunohistochemistry. We identified significant relationships between copper transporter levels and brain copper concentrations, supporting a role for these proteins in copper transport in the human brain. Interestingly, the substantia nigra contained twice as much copper than that in other brain regions, suggesting an important role for copper in this brain region. Furthermore, ATP7A levels were significantly greater in the cerebellum, compared with other brain regions, supporting an important role for ATP7A in cerebellar neuronal health. This study provides novel data regarding copper regulation in the human brain, critical to understand the mechanisms by which brain copper levels can be altered, leading to neurological disease.
Neuroscience Research Australia and The University of New South Wales, Randwick, NSW 2031, Australia. k.davies@neura.edu.au
Katherine M
KM
Davies
Dominic J
DJ
Hare
Veronica
V
Cottam
Nicholas
N
Chen
Leon
L
Hilgers
Glenda
G
Halliday
Julian F B
JF
Mercer
Kay L
KL
Double
D000251:Adenosine Triphosphatases / Q000032:analysis*; D015153:Blotting, Western; D001923:Brain Chemistry; D027682:Cation Transport Proteins / Q000032:analysis*; D003300:Copper / Q000032:analysis*; D000079922:Copper Transport Proteins; D000079923:Copper Transporter 1; D000073840:Copper-Transporting ATPases; D006801:Humans; D007150:Immunohistochemistry; D013058:Mass Spectrometry; D056511:Metallochaperones / Q000032:analysis*; D018832:Molecular Chaperones
C474500:ATOX1 protein, human; D027682:Cation Transport Proteins; D000079922:Copper Transport Proteins; D000079923:Copper Transporter 1; D056511:Metallochaperones; D018832:Molecular Chaperones; D003300:Copper; D000251:Adenosine Triphosphatases; C081184:ATP7A protein, human; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases