Amine oxidase activity of [beta]-amyloid precursor protein modulates systemic and local catecholamine levels

• Published in: Molecular psychiatry Vol. 18; no. 2; p. 245
• Main 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
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group 01.02.2013
• Subjects: Amino acids; Blood pressure; Brain research; Catecholamines; Dopamine; Enzymes; Growth factors; Heart rate; Hormones; Medical research; Mental health; Oxidation; Plasma; Proteins; Psychiatry; United States > US; Australia
• ISSN: 1359-4184; 1476-5578
• DOI: 10.1038/mp.2011.168

The catecholamines dopamine (DA), norepinephrine (NE) and epinephrine (E) are neurotransmitters and hormones that mediate stress responses in tissues and plasma. The expression of [beta]-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=0.27mM), 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.