Moore P, White J, Christiansen V, Grammas P
Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City 73104, USA.
Neurosci Lett. 1998 Sep 18;254(1):29-32. doi: 10.1016/s0304-3940(98)00653-3.
While there is considerable evidence demonstrating altered activity of the major isoforms of protein kinase C (PKC) in the vasculature and neurons of Alzheimer disease (AD) brains, little is known about the activity and/or levels of the atypical PKC isoforms. The objective of this study is to compare PKC-zeta activity and level in cerebral microvessels isolated from AD brains with microvessels from the brains of nondemented age-matched controls. Measurements of the kinase activity reveals that the PKC-zeta activity is significantly (P < 0.01) lower in AD brain microvessels compared with vessels from control brain. Despite this decrease in enzyme activity, the level of PKC-zeta, assessed by Western blot, is significantly (P < 0.01) elevated in AD microvessels. These data demonstrate significant and divergent changes in the PKC-zeta activity and level in the microcirculation of the AD brain and suggest that aberrant regulation of microvascular PKC-zeta could contribute to the abnormal signaling mechanisms at the blood-brain barrier in the AD brain.
虽然有大量证据表明，阿尔茨海默病（AD）患者大脑的血管和神经元中蛋白激酶C（PKC）的主要亚型活性发生了改变，但对于非典型PKC亚型的活性和/或水平却知之甚少。本研究的目的是比较从AD患者大脑中分离出的脑微血管中PKC-ζ的活性和水平与年龄匹配的非痴呆对照者大脑微血管中的情况。激酶活性测量结果显示，与对照者大脑中的血管相比，AD患者脑微血管中的PKC-ζ活性显著降低（P < 0.01）。尽管酶活性有所下降，但通过蛋白质印迹法评估，AD患者微血管中PKC-ζ的水平却显著升高（P < 0.01）。这些数据表明，AD患者大脑微循环中PKC-ζ的活性和水平发生了显著且不同的变化，并提示微血管PKC-ζ的异常调节可能导致AD患者血脑屏障处的信号转导机制异常。
