期刊
MOLECULAR PSYCHIATRY
卷 18, 期 2, 页码 245-254出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/mp.2011.168
关键词
beta-amyloid precursor protein; catecholamines; amine oxidation; neurotransmission
资金
- Australian Research Council
- Australian National Health & Medical Research Council
- Alzheimer's Association
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
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