Attenuated protein kinase C activity and translocation in Alzheimer's disease brain.
Protein kinase C (PKC) activity and its redistribution were determined in postmortem Alzheimer's disease (AD) and age-matched control brains. Cytosolic and membrane-associated PKC activities were lower in frontal and temporal cortices and hippocampi of AD brains. Increased concentrations of phosphatidyl-L-serine, Ca2+ or phorbol 12-myristate, 13-acetate only weakly increased enzyme activity in AD tissues. Redistribution of cytosolic PKC to the membranous fraction was elicited in control brain slices by 162 nM PMA in the presence of K+ (65 mM). This redistribution of the enzyme was markedly reduced in AD brain slices. In contrast, the immunoreactivity of the alpha- and gamma-PKC isozymes were elevated in cortical tissue from AD subjects. No changes were noted in beta-PKC immunoreactivity. These results suggest that the reduced PKC activity and the attenuated translocation of the enzyme in AD brain tissue may be attributed to down regulation of PKC or to alteration in PKC protein. The increase in PKC immunoreactivity may be a reflection of an altered susceptibility to proteolysis or a compensatory response secondary to the loss in enzyme activity.
Wang
H Y
HY
Department of Psychiatry, Medical College of Pennsylvania, Philadelphia 19129.
Pisano
M R
MR
Friedman
E
E
D000368:Aged; D000544:Alzheimer Disease / Q000201:enzymology*; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D010718:Phosphatidylserines / Q000494:pharmacology; D010766:Phosphorylation; D011188:Potassium / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D007527:Isoenzymes; D010718:Phosphatidylserines; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D011188:Potassium