Defective phorbol ester-stimulated secretion of beta-amyloid precursor protein from Alzheimer's disease fibroblasts.
The present study shows that cultured fibroblasts from sporadic Alzheimer's disease patients are deficient in protein kinase C-regulated secretion of amyloid precursor protein. In particular, Alzheimer fibroblasts show a reduced basal secretion and a reduced response at low concentrations of phorbol-12,13-dibutyrate, with an EC50 twofold higher than control fibroblasts. Furthermore, we observed that such defective regulation of the amyloid precursor secretion can possibly be correlated to a specific defect in protein kinase C alpha in fibroblasts from Alzheimer patients.
Bergamaschi
S
S
Institute of Pharmacological Sciences, Universita' di Milano, Italy.
Binetti
G
G
Govoni
S
S
Wetsel
W C
WC
Battaini
F
F
Trabucchi
M
M
Bianchetti
A
A
Racchi
M
M
D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism* / Q000494:pharmacology*; D015153:Blotting, Western; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D012867:Skin / Q000166:cytology / Q000378:metabolism; D013268:Stimulation, Chemical
D016564:Amyloid beta-Protein Precursor; D007527:Isoenzymes; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C