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

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Bibliographic Details
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
Source:	Molecular Psychiatry. Feb2013, Vol. 18 Issue 2, p245-254. 10p. 5 Graphs.
Subjects:	Catecholamines, Amyloid beta-protein, Neurotransmitters, Carrier proteins, Ceruloplasmin
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. [ABSTRACT FROM AUTHOR]
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Database:	Psychology and Behavioral Sciences Collection

Description
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. [ABSTRACT FROM AUTHOR]
ISSN:	13594184
DOI:	10.1038/mp.2011.168