Wang H Y, Pisano M R, Friedman E
Department of Psychiatry, Medical College of Pennsylvania, Philadelphia 19129.
Neurobiol Aging. 1994 May-Jun;15(3):293-8. doi: 10.1016/0197-4580(94)90023-x.
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.
在阿尔茨海默病（AD）患者的死后大脑以及年龄匹配的对照大脑中，测定了蛋白激酶C（PKC）的活性及其重新分布情况。AD大脑额叶和颞叶皮质以及海马体中的胞质和膜相关PKC活性较低。磷脂酰-L-丝氨酸、Ca2+或佛波醇12-肉豆蔻酸酯13-乙酸酯浓度的增加仅微弱地增加了AD组织中的酶活性。在存在K+（65 mM）的情况下，162 nM佛波酯（PMA）可促使对照脑片中的胞质PKC重新分布到膜部分。在AD脑片中，这种酶的重新分布明显减少。相比之下，AD受试者皮质组织中α-PKC和γ-PKC同工酶的免疫反应性升高。β-PKC免疫反应性未观察到变化。这些结果表明，AD脑组织中PKC活性降低和酶的易位减弱可能归因于PKC的下调或PKC蛋白的改变。PKC免疫反应性的增加可能反映了对蛋白水解敏感性的改变或酶活性丧失后的代偿反应。
