Cholinergic agonists and interleukin 1 regulate processing and secretion of the Alzheimer beta/A4 amyloid protein precursor.
Activation of protein kinase C by phorbol esters is known to accelerate the processing and secretion of the beta/A4 amyloid protein precursor. We have now examined various first messengers that increase protein kinase C activity of target cells for their ability to affect beta/A4 amyloid protein precursor metabolism. Acetylcholine and interleukin 1, which are altered in Alzheimer disease, were shown to increase processing of the beta/A4 amyloid protein precursor via the secretory cleavage pathway. Cholinergic agonists stimulated secretion in human glioma and neuroblastoma cells as well as in PC12 cells transfected with the M1 receptor, while interleukin 1 stimulated secretion in human endothelial and glioma cells.
Laboratory of Molecular and Cellular Neuroscience, Rockefeller University, New York, NY 10021.
J D
JD
Buxbaum
M
M
Oishi
H I
HI
Chen
R
R
Pinkas-Kramarski
E A
EA
Jaffe
S E
SE
Gandy
P
P
Greengard
D000109:Acetylcholine / Q000494:pharmacology; D016229:Amyloid beta-Peptides / Q000096:biosynthesis* / Q000302:isolation & purification / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis* / Q000235:genetics / Q000302:isolation & purification; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D018723:Bethanechol; D001626:Bethanechol Compounds / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002460:Cell Line; D002478:Cells, Cultured; D002738:Chloroquine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D007700:Kinetics; D016716:PC12 Cells; D010277:Parasympathomimetics / Q000494:pharmacology*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D014471:Umbilical Veins
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D001626:Bethanechol Compounds; D007375:Interleukin-1; D010277:Parasympathomimetics; D011994:Recombinant Proteins; D018723:Bethanechol; D015240:Phorbol 12,13-Dibutyrate; D001285:Atropine; D002738:Chloroquine; D002217:Carbachol; D011493:Protein Kinase C; D000109:Acetylcholine