蛋白磷酸酶2A活力增高减轻α-突触核蛋白引起的SK-N-SH细胞凋亡  

Activation of protein phosphatase 2A alleviates α-synuclein-induced apoptosis of SK-N-SH cells

作　　者：杨巍巍[1] 杨慧[2] 于顺[1] 

机构地区：[1]首都医科大学宣武医院神经生物学研究室,北京市老年病医疗研究中心分子诊断实验室,教育部神经变性病重点实验室,北京100053 [2]首都医科大学基础医学院神经生物学系,北京脑重大疾病研究院,北京100069

出　　处：《首都医科大学学报》2013年第6期835-839,共5页Journal of Capital Medical University

基　　金：国家重点基础研究发展计划(2011CB504102;2012CB722407);国家自然科学基金(30970940);北京市自然科学基金重点项目(7131001)~~

摘　　要：目的观察蛋白磷酸酶2A(protein phosphatase 2A,PP2A)活力在α-突触核蛋白(α-Syn)引起的细胞凋亡中的作用。方法在SK-N-SH细胞中瞬时转染空载(myc)和α-Syn质粒,免疫荧光化学方法鉴定基因表达情况。Western blotting法和PP2A酶活力检测试剂盒检测PP2A磷酸化水平及酶活力。TUNEL染色和MTT法检测各组细胞死亡情况。结果过表达α-Syn可致磷酸化PP2A(pPP2Ac)水平显著增高及活力降低,同时导致细胞凋亡增多和细胞活力降低。PP2A激动剂C2-ceramide可显著逆转α-Syn所致细胞凋亡。结论 PP2A活力增高可减轻α-Syn过表达引起的细胞凋亡。Objective To explore the role of protein phosphatase 2A （PP2A） activity in o^-Syn-induced cell apoptosis. Methods SK-N-SH cells were transiently transfected with either myc blank vectors or the myc vectors with oL-Syn gene. The expression of ct-Syn gene were indentified by immunofluorescence. The PP2A phosphorylation levels and activity were investigated via Western blotting and Cell PP2A Colorimetric Assay Kit, respectively. TUNEL staining and MTT assay were used to evaluate the cell death. Results Compared with control group, α-Syn overexpression in SK-N-SH cells led to phosphorylation of PP2A（ high pPP2Ac levels） and inhibition of the enzyme activity, α-Syn overexpression also resuhed in the enhancement of apoptotic cells and decrease of cell viable cells. C2- ceramide, the PP2A activator attenuated α-Syn-induced cell death. Conclusion α-Syn enhanced pPP2Ac levels, and inhibited PP2A activity. Activation of endogenous PP2A alleviates α-Syn-induced apoptosis of SK-N-SH cells.

关 键 词：Α-突触核蛋白 蛋白磷酸酶2A 帕金森病 凋亡 

分 类 号：R742.5[医药卫生—神经病学与精神病学]