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Amine oxidase activity of β-amyloid precursor protein modulates systemic and local catecholamine levels.


Duce, JA; Ayton, S; Miller, AA; Tsatsanis, A; Lam, LQ; Leone, L; Corbin, JE; Butzkueven, H; Kilpatrick, TJ; Rogers, JT; Barnham, KJ; Finkelstein, DI; Bush, AI
2013-02
Molecular Psychiatry
Journal Article
18
2
245-254
The catecholamines dopamine (DA), norepinephrine (NE) and epinephrine (E) are neurotransmitters and hormones that mediate stress responses in tissues and plasma. The expression of β-amyloid precursor protein (APP) is responsive to stress and is high in tissues rich in catecholamines. We recently reported that APP is a ferroxidase, subsuming, in neurons and other cells, the iron-export activity that ceruloplasmin mediates in glia. Here we report that, like ceruloplasmin, APP also oxidizes synthetic amines and catecholamines catalytically (K(m) NE=0.27 mM), through a site encompassing its ferroxidase motif and selectively inhibited by zinc. Accordingly, APP knockout mice have significantly higher levels of DA, NE and E in brain, plasma and select tissues. Consistent with this, these animals have increased resting heart rate and systolic blood pressure as well as suppressed prolactin and lymphocyte levels. These findings support a role for APP in extracellular catecholaminergic clearance.
NATURE PUBLISHING GROUP
Amyloid beta-Protein Precursor ; catecholamines ; blood pressure
10.1038/mp.2011.168
© 2013 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.

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Creation Date 2013-02-01 12:00:00