Prostaglandin E2 regulates amyloid precursor protein expression via the EP2 receptor in cultured rat microglia.
We investigated the effects of prostaglandin E2 (PGE2) on amyloid precursor protein (APP) expression in cultured rat microglia. PGE2 treatment significantly increased the expression of APP holoprotein and was associated with an elevation in cyclic AMP (cAMP). Direct activation of adenylate cyclase with forskolin also increased APP expression. Co-treatment of microglia with PGE2 and the PKA inhibitor H-89 suppressed the overexpression of APP caused by PGE2 alone. The prostaglandin EP2 receptor is known to be positively coupled to cAMP production. Stimulation of the EP2 receptor with butaprost increased APP holoprotein, whereas co-incubation of the cells with PGE(2) and the EP2 receptor antagonist AH-6809 blocked the effect of PGE2 on APP expression. These data suggest that PGE2 is able to regulate the expression of APP, and that this effect may be mediated by the EP2 receptor and the cAMP signaling cascade.
Pooler
Amy M
AM
Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Arjona
Anibal A
AA
Lee
Robert K
RK
Wurtman
Richard J
RJ
D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis*; D000818:Animals; D002478:Cells, Cultured; D015232:Dinoprostone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D018078:Receptors, Prostaglandin E / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D058307:Receptors, Prostaglandin E, EP2 Subtype; D044004:Xanthones / Q000494:pharmacology
D016564:Amyloid beta-Protein Precursor; C545646:Ptger2 protein, rat; D018078:Receptors, Prostaglandin E; D058307:Receptors, Prostaglandin E, EP2 Subtype; D044004:Xanthones; C053876:6-isopropoxy-9-oxoxanthene-2-carboxylic acid; D015232:Dinoprostone