蛋白磷酸酶2A催化亚基C在小鼠脑与阿尔茨海默病患者脑中的表达

摘要

目的 为了研究蛋白磷酸酶2A催化亚基C(PP2AC)在中枢神经系统中的功能与疾病相关性,探讨其在小鼠脑中与阿尔茨海默病患者脑中的表达情况.方法 应用成年野生型小鼠全身组织、不同年龄野生型小鼠脑组织;阿尔茨海默病患者与正常人的额叶皮质,分别制作石蜡切片和提取组织蛋白.通过免疫组织化学染色检测PP2AC在小鼠各年龄不同脑区和阿尔茨海默病患者及正常人脑样本中的表达;应用免疫印迹法检测PP2AC在小鼠全身各器官和各年龄段大脑皮质中的表达.结果 在成年小鼠各器官中,PP2AC在中枢神经系统中的表达丰度最高;从胚胎第18.5天到出生后2年的小鼠脑组织中PP2AC在不同脑区呈显著的时空特异性表达模式,且PP2AC在大脑皮质呈年龄相关性表达升高的趋势.与正常人样本相比较,阿尔茨海默病患者额叶皮质中Aβ1-42表达和Tau蛋白磷酸化水平升高,而PP2AC明显减少.结论 PP2AC在小鼠脑中以及在阿尔茨海默病患者脑中表达降低的时空特异性表达模式,提示PP2AC在中枢神经系统中有重要作用,且PP2AC表达下降可能与阿尔茨海默病相关.%Objective To investigate the biological functions of protein phosphatase 2AC( PP2AC) in the brain, and to detect its spatio-temporal expression and its involvement in neurological disorders in the brains of mice and Alzheimer′s patients. Methods Western blot was used to evaluate the expression level of PP2AC in different organs. Immunohistochemical staining was performed to detect the in situ expression levels of PP2AC in the brains of mice and patients, and the pathological changes were confirmed in the brains of patients with Alzheimer′s disease. Results Among all the tested organs in adult mouse, the expression of PP2AC protein was the highest in the brain. From embryonic day 18. 5 to postnatal 2-year-old mice, PP2AC exhibited spatio-temporal specific expression in the brains. Furthermore, an age-dependent increased expression in the cerebral cortex at both protein and RNA levels was observed. Compared to control group, PP2AC protein expression was lower in the frontal cortex of Alzheimer′s patients. Conclusions The spatio-temporal specific expression profiles of PP2AC in mouse brain implicate its biological significance. Its diminished expression in the frontal cortex of Alzheimer′s disease patients implies that PP2AC plays a potential role in the pathogenesis of Alzheimer′s disease.