PRMT1介导的EZH2甲基化通过靶向抑制SOCS3促进帕金森病发生和发展  

PRMT1-mediated methylation in EZH2 promoted the occurrence and development of Parkinson's disease via inhibiting SOCS3

作　　者：冯丹 刘韵 左方娅 刘纷纷 郭修红 刘钰淇 陈兰兰 王玉洁 田锦勇[4] FENG Dan;LIU Yun;ZUO Fangya;LIU Fenfen;GUO Xiuhong;LIU Yuqi;CHEN Lanlan;WANG Yujie;TIAN Jinyong(Guizhou University of Traditional Chinese Medicine,Guiyang 550001,China;不详)

机构地区：[1]贵州中医药大学,贵阳550001 [2]清镇市第一人民医院重症医学科 [3]遵义医科大学 [4]贵州省人民医院全科医学科

出　　处：《临床神经外科杂志》2025年第1期61-68,共8页Journal of Clinical Neurosurgery

基　　金：贵州省科技厅2020年基础研究重大项目[黔科合基础(2020)1Z059]。

摘　　要：目的探究精氨酸甲基转移酶1(PRMT1)通过调味增强子同源物2(EZH2)调控细胞因子信号抑制因子3(SOCS3)介导的帕金森病(PD)机制。方法以小鼠多巴胺能神经元细胞为研究对象,采用1-甲基-4-苯基吡啶离子(MPP^(+))建立PD体外细胞模型。将小鼠多巴胺能神经元细胞分为对照组、MPP^(+)组、MPP^(+)+si-NC组、MPP^(+)+si-PRMT1组、MPP^(+)+si-PRMT1+oe-NC组、MPP^(+)+si-PRMT1+oe-EZH2组。观察各组细胞在细胞凋亡、细胞活力、EZH2在SOCS3启动子上的富集程度、PRMT1、EZH2、SOCS3、pT311-EZH2方面的表达。结果MPP^(+)组细胞凋亡率高于对照组(P<0.05),而细胞活力低于对照组(P<0.05)。MPP^(+)组EZH2在SOCS3启动子上的富集程度显著高于对照组,且PRMT1及EZH2表达高于对照组(P<0.05),SOCS3及pT311-EZH2低于对照组。MPP^(+)+si-PRMT1组细胞凋亡率低于MPP^(+)+si-NC组(P<0.05),但细胞活力高于MPP^(+)+si-NC组(P<0.05)。MPP^(+)+si-PRMT1组EZH2在SOCS3启动子上的富集程度少于MPP^(+)+si-NC组,PRMT1及EZH2表达低于MPP^(+)+si-NC组(P<0.05),但SOCS3及pT311-EZH2表达高于MPP^(+)+si-NC组(P<0.05)。MPP^(+)+si-PRMT1+oe-EZH2组EZH2高于MPP^(+)+si-PRMT1+oe-NC组(P<0.05),而SOCS3低于MPP^(+)+si-PRMT1+oe-NC(P<0.05)。MPP^(+)+si-PRMT1+oe-EZH2组细胞凋亡率高于MPP^(+)+si-PRMT1+oe-NC组(P<0.05),但细胞活力低于MPP^(+)+si-PRMT1+oe-NC组(P<0.05)。结论PRMT1通过抑制EZH2蛋白T311残基磷酸化增强EZH2稳定性,进而下调SOCS3,引起PD中多巴胺能神经元细胞死亡,促进PD发生和发展。Objective To reveal protein arginine methyltransferase 1(PRMT1)regulates suppressor of cytokine signaling 3(SOCS3)-mediated pathology of Parkinson' disease(PD)via Enhancer of zeste homolog 2(EZH2).Methods In this study,mouse dopaminergic neuronal cells were incubated with 1-methyl-4-phenylpyridiniumion(MPP^(+))to mimic PD in vitro.Mouse dopaminergic neuronal cells were divided into control,MPP^(+),MPP^(+)+si-NC,MPP^(+)+si-PRMT1,MPP^(+)+si-PRMT1+oe-NC and MPP^(+)+si-PRMT1+oe-EZH2 group.The changes in apoptosis,viability,enrichment of EZH2 in SOCS3,PRMT1,EZH2,SOCS3 and pT311-EZH2 in the six groups were compared.Results Compared to control group,MPP^(+)group developed the increases in apoptosis,PRMT1,EZH2 and enrichment of EZH2,and the decreases in cel viability,SOCS3 and p-T311-EZH2.Compared to MPP^(+)+si-NC group,MPP^(+)+si-PRMT1 group showed the reductions in apoptosis,PRMT1,EZH2 and enrichment of EZH2,and the elevations in cell viability,SOCS3 and p-T311-EZH2.Compared to MPP^(+)+si-PRMT1+oe-NC group,MPP^(+)+si-PRMT1+oe-EZH2 group displayed the enhancement of apoptosis and EZH2 and the decline in SOCS3 and cell viability.Conclusions PRMT1 stabilizes EZH2 via inhibiting the phosphorylation of Thr311 located in EZH2,thereby downregulating SOCS3 to induce the death in dopaminergic neuronal cells during PD,so as to promoted the occurrence and development of D.

关 键 词：帕金森病 细胞因子信号抑制因子3 精氨酸甲基转移酶1 调味增强子同源物2 

分 类 号：R742.5[医药卫生—神经病学与精神病学]