Title |
Amine oxidase activity of β-amyloid precursor protein modulates systemic and local catecholamine levels
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Published in |
Molecular Psychiatry, January 2012
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DOI | 10.1038/mp.2011.168 |
Pubmed ID | |
Authors |
J A Duce, S Ayton, A A Miller, A Tsatsanis, L Q Lam, L Leone, J E Corbin, H Butzkueven, T J Kilpatrick, J T Rogers, K J Barnham, D I Finkelstein, A I Bush |
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 (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. |
X Demographics
Geographical breakdown
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Unknown | 1 | 100% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 28 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 5 | 18% |
Researcher | 3 | 11% |
Student > Bachelor | 2 | 7% |
Other | 2 | 7% |
Professor > Associate Professor | 2 | 7% |
Other | 6 | 21% |
Unknown | 8 | 29% |
Readers by discipline | Count | As % |
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Agricultural and Biological Sciences | 5 | 18% |
Psychology | 4 | 14% |
Neuroscience | 3 | 11% |
Medicine and Dentistry | 3 | 11% |
Sports and Recreations | 1 | 4% |
Other | 3 | 11% |
Unknown | 9 | 32% |