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Ca 2+ ‐Dependent and Ca 2+ ‐Independent Protein Kinase C Changes in the Brains of Patients with Alzheimer's Disease
Author(s) -
Matsushima Hideyuki,
Shimohama Shun,
Chachin Motohiko,
Taniguchi Takashi,
Kimura Jun
Publication year - 1996
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1996.67010317.x
Subject(s) - protein kinase c , cytosol , phosphatidylinositol , isozyme , cardiolipin , medicine , endocrinology , pkc alpha , alzheimer's disease , chemistry , biology , enzyme , signal transduction , microbiology and biotechnology , biochemistry , disease , phospholipid , membrane
We examined protein kinase C (PKC) activity in Ca 2+ ‐dependent PKC (Ca 2+ ‐dependent PKC activities) and Ca 2+ ‐independent PKC (Ca 2+ ‐independent PKC activities) assay conditions in brains from Alzheimer's disease (AD) patients and age‐matched controls. In cytosolic and membranous fractions, Ca 2+ ‐dependent and Ca 2+ ‐independent PKC activities were significantly lower in AD brain than in control brain. In particular, reduction of Ca 2+ ‐independent PKC activity in the membranous fraction of AD brain was most enhanced when cardiolipin, the optimal stimulator of PKC‐ε, was used in the assay; whereas Ca 2+ ‐independent PKC activity stimulated by phosphatidylinositol, the optimal stimulator of PKC‐δ, was not significantly reduced in AD. Further studies on the protein levels of Ca 2+ ‐independent PKC‐δ, PKC‐ε, and PKC‐ζ in AD brain revealed reduction of the PKC‐ε level in both cytosolic and membranous fractions, although PKC‐δ and PKC‐ζ levels were not changed. These findings indicated that Ca 2+ ‐dependent and Ca 2+ ‐independent PKC are changed in AD, and that among Ca 2+ ‐independent PKC isozymes, the alteration of PKC‐ε is a specific event in AD brain, suggesting its crucial role in AD pathophysiology.