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- Title
Amine oxidase activity of β-amyloid precursor protein modulates systemic and local catecholamine levels.
- Authors
Duce, J A; Ayton, S; Miller, A A; Tsatsanis, A; Lam, L Q; Leone, L; Corbin, J E; Butzkueven, H; Kilpatrick, T J; Rogers, J T; Barnham, K J; Finkelstein, D I; Bush, A I
- Abstract
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 (Km 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.
- Subjects
CATECHOLAMINES; AMYLOID beta-protein; NEUROTRANSMITTERS; CARRIER proteins; CERULOPLASMIN
- Publication
Molecular Psychiatry, 2013, Vol 18, Issue 2, p245
- ISSN
1359-4184
- Publication type
Article
- DOI
10.1038/mp.2011.168