Cornel iridoid glycoside inhibits PP2Ac demethylation by regulationg PME-1  

作　　者：YANG Cui-cui KUAI Xue-xian LI Ya-li ZHANG Li LI Lin ZHANG Lan 

机构地区：[1]Department of Pharmacology,Xuanwu Hospital of Capital Medical University,Key Laboratory for Neu-rodegenerative Diseases of Ministry of Education,Beijing 100053,China

出　　处：《中国药理学与毒理学杂志》2021年第9期656-656,共1页Chinese Journal of Pharmacology and Toxicology

摘　　要：OBJECTIVE PP2Ac demethyl⁃ation is regulated by LCMT(a specific leucine carboxyl methyltransferase catalyzing methyla⁃tion of PP2A)and PME(a specific methylester⁃ase catalyzing demethylation of PP2A.This study was to investigate the mechanism of Cor⁃nel iridoid glycoside(CIG)on PP2A catalytic sub⁃unit C(PP2Ac).METHODS Recombined lentivi⁃rus vector was used to deliver PME-1 genetic materials into N2a cells or transfected LCMT-1 siRNA into N2a cells to block the expression of LCMT-1.Twenty-four hours later,cells were rinsed twice with cold PBS(pH 7.4)and CIG at different concentrations(50,100 and 200 g·L^(-1),respectively)were added for 24 h.Western blotting was used to PP2Ac,demethylaion/methylation PP2Ac,LCMT-1 and PME-1.The ac⁃tivity of PP2A was detected by a biochemical as⁃say.RESULTS①Lentivirus transferred PME-1 was expressed at high level in the N2a cells after transduction.Correspondingly,the demethylation of PP2Ac was increasing and PP2A activity was decreasing after transduction.Treatment with CIG for 24 h reversed the increase of PME-1 and demethylation of PP2Ac without influencing LCMT-1 expression.PP2A activity was also sig⁃nificantly enhanced in CIG treatment group,compared with the cells after PME-1 transduc⁃tion.②LCMT-1 siRNA significantly decreased LCMT-1 expression.CIG did not affect LCMT-1expression.however,demethylation of PP2Ac is increased in siRNA-transfected cells and CIG could reversed the high demethylation of PP2Ac and PP2A activity.CONLUSION CIG increases methylation of PP2A subunit C by inhibiting PME-1.

关 键 词：cornel iridoid glycoside Alzheimer disease PP2A catalytic subunit C demethylation 

分 类 号：R749.16[医药卫生—神经病学与精神病学]