Matsushima H, Shimohama S, Chachin M, Taniguchi T, Kimura J
Department of Neurology, Faculty of Medicine, Kyoto University, Kyoto, Japan.
J Neurochem. 1996 Jul;67(1):317-23. doi: 10.1046/j.1471-4159.1996.67010317.x.
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.
我们在阿尔茨海默病（AD）患者及年龄匹配的对照者大脑中，于钙离子依赖型蛋白激酶C（Ca2+依赖型PKC活性）和钙离子非依赖型蛋白激酶C（Ca2+非依赖型PKC活性）的检测条件下，检测了蛋白激酶C（PKC）活性。在胞质和膜组分中，AD大脑中Ca2+依赖型和Ca2+非依赖型PKC活性均显著低于对照大脑。特别是，当使用心磷脂（PKC-ε的最佳刺激物）进行检测时，AD大脑膜组分中Ca2+非依赖型PKC活性的降低最为明显；而由磷脂酰肌醇（PKC-δ的最佳刺激物）刺激的Ca2+非依赖型PKC活性在AD中未显著降低。对AD大脑中Ca2+非依赖型PKC-δ、PKC-ε和PKC-ζ蛋白水平的进一步研究显示，尽管PKC-δ和PKC-ζ水平未改变，但胞质和膜组分中PKC-ε水平均降低。这些发现表明，AD中Ca2+依赖型和Ca2+非依赖型PKC均发生了变化，并且在Ca2+非依赖型PKC同工酶中，PKC-ε的改变是AD大脑中的一个特定事件，提示其在AD病理生理学中起关键作用。
