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

作者：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^*

来源：Molecular Psychiatry, 2013, 18(2): 245-254.

DOI：10.1038/mp.2011.168

• beta-amyloid precursor protein
• catecholamines
• amine oxidation
• neurotransmission

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. Molecular Psychiatry (2013) 18, 245-254; doi:10.1038/mp.2011.168; published online 3 January 2012

• 出版日期2013-2
• 单位河北医科大学