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)

Full text not currently available from Enlighten.

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 > School of Cardiovascular & Metabolic Health
Journal Name:Molecular Psychiatry
Publisher:Nature Publishing Group
ISSN:1359-4184
ISSN (Online):1476-5578
Published Online:03 January 2012

University Staff: Request a correction | Enlighten Editors: Update this record