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

Duce, J.A. et al. (2013) Amine oxidase activity of β-amyloid precursor protein modulates systemic and local catecholamine levels. Molecular Psychiatry, 18(2), pp. 245-254. (doi: 10.1038/mp.2011.168) (PMID:22212595)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Miller, Dr Alyson
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., and Bush, A.I.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Molecular Psychiatry
Publisher:Nature Publishing Group
ISSN:1359-4184
ISSN (Online):1476-5578
Published Online:03 January 2012

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