Wagey R, Pelech S L, Duronio V, Krieger C
Department of Medicine, University of British Columbia, Vancouver, Canada.
J Neurochem. 1998 Aug;71(2):716-22. doi: 10.1046/j.1471-4159.1998.71020716.x.
Enzyme activities and protein levels of several protein and lipid kinases were measured in postmortem tissue from patients who died with amyotrophic lateral sclerosis (ALS) as well as from control subjects. Patients who died with ALS had increased activities and protein levels of phosphatidylinositol 3-kinase (PI 3-K) in particulate fractions of spinal cord tissue compared with control subjects. The PI 3-K activity increased with PI 3-K protein level, indicating no change in specific PI 3-K activity in ALS. No differences in PI 3-K activities were found in cytosolic fractions of spinal cord, or in motor and visual cortices, from ALS patients compared with those from controls. PI 3-K activities and protein levels were unchanged in brain tissue from patients who died with Alzheimer's disease compared with those from controls. PI 3-K is a lipid kinase that is important for cell survival and is activated in response to many growth factors. Increased PI 3-K activities in particulate fractions of spinal cord from ALS patients may be related to the increase of PI 3-K protein levels found in this tissue. The protein kinases Erk2, protein kinase B (PKB), and p70 ribosomal S6 kinase (S6K) showed no differences in activities in spinal cord tissue between ALS patients and controls. However, the amounts of PKB and S6K protein were significantly higher in ALS patients, whereas Erk2 protein amount was unchanged compared with controls. Protein kinase C activity was increased in spinal cord tissue from ALS patients, which is consistent with our previous report. The increased activity of PI 3-K in spinal cord tissue from patients with ALS implicates the involvement or activation of PI 3-K in ALS, as either a cause or a consequence of the neuron loss. The lack of up-regulation in the activities of PKB and S6K in ALS tissue supports an impairment in signal transduction cascades mediated by PI 3-K in this neurodegenerative disease.
在死于肌萎缩侧索硬化症（ALS）的患者以及对照受试者的死后组织中，检测了几种蛋白质和脂质激酶的酶活性及蛋白质水平。与对照受试者相比，死于ALS的患者脊髓组织颗粒部分中磷脂酰肌醇3激酶（PI 3-K）的活性和蛋白质水平有所升高。PI 3-K活性随PI 3-K蛋白质水平增加，表明ALS中PI 3-K的比活性没有变化。与对照组相比，ALS患者脊髓的胞质部分、运动皮层和视觉皮层中PI 3-K活性没有差异。与对照组相比，死于阿尔茨海默病的患者脑组织中PI 3-K活性和蛋白质水平没有变化。PI 3-K是一种脂质激酶，对细胞存活很重要，可响应多种生长因子而被激活。ALS患者脊髓颗粒部分中PI 3-K活性增加可能与该组织中PI 3-K蛋白质水平升高有关。蛋白质激酶Erk2、蛋白激酶B（PKB）和p70核糖体S6激酶（S6K）在ALS患者和对照者的脊髓组织中的活性没有差异。然而，与对照组相比，ALS患者中PKB和S6K蛋白质的量显著更高，而Erk2蛋白质的量没有变化。ALS患者脊髓组织中蛋白激酶C活性增加，这与我们之前的报告一致。ALS患者脊髓组织中PI 3-K活性增加表明PI 3-K参与或激活了ALS，可能是神经元丢失的原因或结果。ALS组织中PKB和S6K活性缺乏上调支持了在这种神经退行性疾病中由PI 3-K介导的信号转导级联受损。
