Amine oxidase activity of ß-amyloid precursor protein modulates systemic and local catecholamine levels.
Mol Psychiatry
; 18(2): 245-54, 2013 Feb.
Article
em En
| MEDLINE
| ID: mdl-22212595
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 ß-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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Catecolaminas
/
Precursor de Proteína beta-Amiloide
/
Monoaminoxidase
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Mol Psychiatry
Ano de publicação:
2013
Tipo de documento:
Article