Reduced protein kinase C activity in sporadic Alzheimer's disease fibroblasts.
A decrease in the protein kinase C immunoreactivity and an altered protein phosphorylation have been reported in patients with Alzheimer's disease, but discordant results have been obtained from determinations of protein kinase C activity. By assaying the calcium- and phospholipid-dependent phosphorylation of a lysine-rich histone after detergent extraction, we have determined the total protein kinase C activity in fibroblasts from patients with sporadic Alzheimer's disease, age-matched controls and young subjects. The activity was not significantly different between young and aged controls, whereas it was significantly lower (0.70 +/- 0.12 vs 1.16 +/- 0.23 nmol/min/mg protein, P less than 0.01) in the patients. The total amount of protein kinase C estimated from the binding of phorbol dibutyrate to intact cells was also significantly lower (1.70 +/- 0.41 vs 2.48 +/- 0.54 pmol/mg protein, P less than 0.01). This decrease in protein kinase C activity suggests that abnormal protein phosphorylation might play a role in the pathogenesis of the disease.
Bruel
A
A
Laboratoire de Biochimie Génétique, CNRS URA 1335, Hôpital des Enfants Malades, Paris, France.
Cherqui
G
G
Columelli
S
S
Margelin
D
D
Roudier
M
M
Sinet
P M
PM
Prieur
M
M
Pérignon
J L
JL
Delabar
J
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology*; D002648:Child; D002675:Child, Preschool; D005347:Fibroblasts / Q000201:enzymology*; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D008875:Middle Aged; D015240:Phorbol 12,13-Dibutyrate / Q000378:metabolism; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*
D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C