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. © 2013 Macmillan Publishers Limited.
CITATION STYLE
Duce, J. A., Ayton, S., Miller, A. A., Tsatsanis, A., Lam, L. Q., Leone, L., … Bush, A. I. (2013). Amine oxidase activity of β-amyloid precursor protein modulates systemic and local catecholamine levels. Molecular Psychiatry, 18(2), 245–254. https://doi.org/10.1038/mp.2011.168
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