REDUCED PROTEIN-KINASE-C ACTIVITY IN SPORADIC ALZHEIMERS-DISEASE FIBROBLASTS
REDUCED PROTEIN-KINASE-C ACTIVITY IN SPORADIC ALZHEIMERS-DISEASE FIBROBLASTS
复制标题
DOI：
10.1016/0304-3940(91)90064-z
复制
发表时间：
1991-11-25
影响因子：
2.5
通讯作者：
DELABAR, J
中科院分区：
文献类型：
--
作者：
BRUEL, A;CHERQUI, G;DELABAR, J
据报道，阿尔茨海默病患者的蛋白激酶C免疫反应性降低，蛋白磷酸化改变，但从蛋白激酶C活性测定中获得了不一致的结果。通过测定钙和磷脂依赖性磷酸化的赖氨酸丰富的组蛋白洗涤剂提取后，我们已经确定了总蛋白激酶C活性的成纤维细胞从散发性阿尔茨海默氏病患者，年龄匹配的控制和年轻的主题。年轻和老年对照组之间的活性没有显著差异，而患者的活性显著降低（0.70 +/- 0.12 vs 1.16 +/- 0.23 nmol/min/mg蛋白，P < 0.01）。从佛波醇二丁酸酯与完整细胞的结合估计的蛋白激酶C的总量也显著较低（1.70 +/- 0.41 vs 2.48 +/- 0.54 pmol/mg蛋白，P < 0.01）。这种蛋白激酶C活性的降低表明异常的蛋白磷酸化可能在疾病的发病机制中起作用。
A decrease in the protein kinase C immunoreactivity and an altered protein phosphorylation have been reported in patients with Alzheimer's disease, but discordant results have been obtained from determinations of protein kinase C activity. By assaying the calcium- and phospholipid-dependent phosphorylation of a lysine-rich histone after detergent extraction, we have determined the total protein kinase C activity in fibroblasts from patients with sporadic Alzheimer's disease, age-matched controls and young subjects. The activity was not significantly different between young and aged controls, whereas it was significantly lower (0.70 +/- 0.12 vs 1.16 +/- 0.23 nmol/min/mg protein, P < 0.01) in the patients. The total amount of protein kinase C estimated from the binding of phorbol dibutyrate to intact cells was also significantly lower (1.70 +/- 0.41 vs 2.48 +/- 0.54 pmol/mg protein, P < 0.01). This decrease in protein kinase C activity suggests that abnormal protein phosphorylation might play a role in the pathogenesis of the disease.