Specific role for protein kinase C alpha in the constitutive and regulated secretion of amyloid precursor protein in human skin fibroblasts.
Reduced levels of protein kinase C alpha (PKC alpha) seems to be related to an altered amyloid precursor protein (APP) secretion in fibroblasts from Alzheimer's disease (AD) patients. In this report we used a specific inhibitor of PKC alpha (Gö-6976), to investigate the role of PKC alpha in the basal and phorbol esters regulated secretion of soluble APP (sAPP) in human fibroblasts derived from healthy aged volunteers. Treatment with Gö-6976 alone reduced basal secretion by a maximum of 39%, compared to untreated cells, suggesting the partial dependence of constitutive APP secretory pathway on PKC alpha enzyme. Moreover Gö-6976 treatment completely abolished the effect of phorbol-esters mediated PKC stimulation on sAPP release, suggesting that PKC alpha is the only PKC isoform involved in controlling the secretion of sAPP in human fibroblasts.
Benussi
L
L
Laboratory of Cellular and Molecular Neurobiology, Alzheimer's Disease Unit, I.R.C.C.S. Centro San Giovanni di Dio-Fatebnefratelli, Brescia, Italy.
Govoni
S
S
Gasparini
L
L
Binetti
G
G
Trabucchi
M
M
Bianchetti
A
A
Racchi
M
M
D000368:Aged; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D001706:Biopsy; D015152:Blotting, Northern; D015153:Blotting, Western; D002227:Carbazoles / Q000494:pharmacology; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D051571:Protein Kinase C-alpha; D012867:Skin / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism*; D019311:Staurosporine / Q000494:pharmacology
D016564:Amyloid beta-Protein Precursor; D002227:Carbazoles; D007211:Indoles; D007527:Isoenzymes; C081021:Go 6976; D015240:Phorbol 12,13-Dibutyrate; C496628:PRKCA protein, human; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D019311:Staurosporine