Ca2+-dependent and Ca2+-independent protein kinase C changes in the brain of patients with Alzheimer's disease.
We examined protein kinase C (PKC) activity in Ca2+-dependent PKC (Ca2+-dependent PKC activities) and Ca2+-independent PKC (Ca2+-independent PKC activities) assay conditions in brains from Alzheimer's disease (AD) patients and age-matched controls. In cytosolic and membranous fractions, Ca2+-dependent and Ca2+-independent PKC activities were significantly lower in AD brain than in control brain. In particular, reduction of Ca2+-independent PKC activity in the membranous fraction of AD brain was most enhanced when cardiolipin, the optimal stimulator of PKC-epsilon, was used in the assay; whereas Ca2+-independent PKC activity stimulated by phosphatidylinositol, the optimal stimulator of PKC-delta, was not significantly reduced in AD. Further studies on the protein levels of Ca2+-independent PKC-delta, PKC-epsilon and PKC-zeta in AD brain revealed reduction of the PKC-epsilon level in both cytosolic and membranous fractions, although PKC-delta and PKC-zeta levels were not changed. These findings indicated that Ca2+-dependent and Ca2+-independent PKC are changed in AD, and that among Ca2+-independent PKC isozymes, the alteration of PKC-epsilon is a specific event in AD brain, suggesting its crucial role in AD pathophysiology.
Matsushima
H
H
Department of Neurology, Faculty of Medicine, Kyoto University, Kyoto, Japan.
Shimohama
S
S
Chachin
M
M
Taniguchi
T
T
Kimura
J
J
D000544:Alzheimer Disease / Q000201:enzymology*; D000818:Animals; D001344:Autopsy; D001921:Brain / Q000166:cytology / Q000201:enzymology*; D002118:Calcium / Q000502:physiology*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D009474:Neurons / Q000201:enzymology; D011493:Protein Kinase C / Q000378:metabolism*; D051745:Protein Kinase C-delta; D051744:Protein Kinase C-epsilon; D051381:Rats; D013997:Time Factors; D000099221:Protein Kinase C zeta
D002118:Calcium; D007527:Isoenzymes; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; D051744:Protein Kinase C-epsilon; D000099221:Protein Kinase C zeta; C497260:Prkcd protein, rat; C497257:Prkce protein, rat; C497258:PRKCD protein, human; C497255:PRKCE protein, human