Lanius R A, Paddon H B, Mezei M, Wagey R, Krieger C, Pelech S L, Shaw C A
Neuroscience Programme, University of British Columbia, Vancouver, Canada.
J Neurochem. 1995 Aug;65(2):927-30. doi: 10.1046/j.1471-4159.1995.65020927.x.
Amyotrophic lateral sclerosis (ALS) is a human neurodegenerative disorder of unknown origin that is characterized by progressive degeneration of corticospinal tracts and anterior horn cells in the brainstem and spinal cord. Previous studies have indicated that motoneuron degeneration associated with ALS may be triggered by mechanisms leading to increased intracellular Ca2+. In the present report, Ca(2+)-activated phospholipid-dependent protein kinase C (PKC) was evaluated in cervical spinal cords from ALS patients and control subjects. In patients who died with ALS, PKC histone H1 phosphotransferase activity was significantly increased by 330% in cytosolic- and 118% in particulate-derived extracts compared with controls. This increase in PKC phosphotransferase activity appeared to be partially due to an increase in the amount of PKC protein present in ALS spinal cord tissue. PKC histone H1 phosphotransferase activities of cytosolic- and particulate-derived extracts from motor and visual cortex of ALS patients and controls were not statistically different, nor were there differences in PKC histone H1 phosphotransferase activity in platelets and leukocytes. The specific nature of PKC alterations in affected regions of the CNS supports a role for PKC in the events leading to motoneuron death in sporadic ALS.
肌萎缩侧索硬化症（ALS）是一种病因不明的人类神经退行性疾病，其特征是脑干和脊髓中的皮质脊髓束和前角细胞进行性退化。先前的研究表明，与ALS相关的运动神经元退化可能由导致细胞内Ca2+增加的机制触发。在本报告中，对ALS患者和对照受试者的颈脊髓中的Ca(2+)激活的磷脂依赖性蛋白激酶C（PKC）进行了评估。在死于ALS的患者中，与对照组相比，胞质提取物中的PKC组蛋白H1磷酸转移酶活性显著增加了330%，颗粒提取物中的活性增加了118%。PKC磷酸转移酶活性的这种增加似乎部分是由于ALS脊髓组织中PKC蛋白量的增加。ALS患者和对照受试者的运动和视觉皮层的胞质和颗粒提取物中的PKC组蛋白H1磷酸转移酶活性没有统计学差异，血小板和白细胞中的PKC组蛋白H1磷酸转移酶活性也没有差异。中枢神经系统受影响区域PKC改变的特异性支持PKC在散发性ALS导致运动神经元死亡的事件中起作用。
