PGC-1α基因在HIV-1包膜糖蛋白gp120诱导神经元线粒体功能障碍中的作用及机制研究  

Role and Mechanism of Action of the PGC-1α Gene in HIV-1 Glycoprotein Gp120-induced Mitochondrial Dysfunction in Neurons

作　　者：王星[1] 刘江福[1] 杨鹏雅[1] 何秀华[1] 李由 WANG Xing;LIU Jiangfu;YANG Pengya;HE Xiuhua;LI You(Quanzhou No.1 Hospital Affiliated to Fujian Medical University,Quanzhou 362000,China)

机构地区：[1]福建医科大学附属泉州第一医院,泉州362000

出　　处：《病毒学报》2021年第6期1348-1354,共7页Chinese Journal of Virology

摘　　要：人类免疫缺陷病毒(Human immunodeficiency viru,HIV)包膜糖蛋白gp120具有神经毒性,可引起神经元损伤,与HIV相关性痴呆的发生有关,但gp120引起神经元损伤的机制尚不清楚。有研究报道gp120能够引起神经元出现线粒体功能障碍,而PGC-1α是促进神经元内线粒体生成的关键基因。因此,本研究将分析PGC-1α基因在HIV-1包膜糖蛋白gp120诱导神经元线粒体功能障碍中的作用及机制。原代培养皮层神经元细胞后分为对照组、gp120组、空白质粒组、gp120+空白质粒组,gp120+PGC-1α质粒组、PGC-1α质粒组,检测细胞活力OD_(490 nm)、线粒体膜电位(△ψm)水平、三磷酸腺苷(ATP)含量、活性氧簇(ROS)含量、凋亡率及PGC-1α、cleaved caspase-9、cleaved caspase-3的表达水平。结果显示,gp120组皮层神经元的PGC-1α表达水平、OD_(490 nm)水平、△ψm水平、ATP含量均低于对照组,ROS含量、凋亡率、cleaved caspase-9、cleaved caspase-3的表达水平均高于对照组;过表达PGC-1α后,gp120+PGC-1α质粒组皮层神经元的PGC-1α表达水平、OD_(490 nm)水平、△ψm水平、ATP含量均高于gp120+空白质粒组,ROS含量、凋亡率、cleaved caspase-9、cleaved caspase-3的表达水平均低于gp120+空白质粒组。以上结果表明,gp120诱导皮层神经元出现线粒体氧化呼吸功能减退、线粒体途径凋亡等线粒体功能障碍的表现,抑制PGC-1α基因表达是gp120诱导线粒体功能障碍的相关机制之一。本研究的创新点在于探究了gp120诱导神经元线粒体功能障碍的分子机制,研究发现抑制PGC-1α基因表达是gp120诱导神经元线粒体功能障碍的相关机制之一,这为今后阐明gp120诱导神经元损伤及HIV相关性痴呆的发病机制提供了实验依据。Glycoprotein gp120 in the human immunodeficiency virus(HIV)envelope can cause neuron damage,which is related to HIV-related dementia. However,the mechanism of gp120-induced neuronal damage is not clear. It has been reported that gp120 can cause mitochondrial dysfunction in neurons,and that PGC-1α is the key gene to promote mitochondrial production in neurons. We investigated the role and mechanism of action of the PGC-1α gene in HIV-1 glycoprotein gp120-induced dysfunction of mitochondria in neurons. Primary cortical neurons were cultured and divided into the control group,gp120 group,blank plasmid group,gp120+blank plasmid group, gp120+PGC - 1α plasmid group, and PGC - 1α plasmid group. The level of OD_(490 nm),mitochondrial membrane potential(△ ψm),adenosine triphosphate(ATP)content,reactive oxygen species(ROS)content,apoptosis percentage as well as expression of PGC-1α,cleaved caspase-9 and cleaved caspase-3 were measured. We discovered that PGC-1α expression,OD;level,△ψm and ATP content in the cortical neurons of the gp120 group were lower than those of the control group,and that the ROS content,apoptosis percentage,as well as expression of cleaved caspase - 9 and cleaved caspase - 3 were higher than those of the control group. After PGC-1α overexpression,PGC-1α expression,OD;level,△ψm and ATP content in the cortical neurons of the gp120+PGC - 1α plasmid group were higher than those of the gp120+blank plasmid group,and ROS content,apoptosis percentage,as well as expression of cleaved caspase-9 and cleaved caspase-3 were lower than those of the gp120+blank plasmid group. These results showed that gp120 induced mitochondrial dysfunction,including oxidative respiratory dysfunction and inhibition of pathways. Inhibition of expression of the PGC - 1α gene appeared to be one of the mechanisms of gp120 - induced mitochondrial dysfunction. The innovation of our study was to explore the molecular mechanism of gp120-induced dysfunction of the mitochondria in neurons. Our study provides an experimenta

关 键 词：人类免疫缺陷病毒(HIV) 包膜糖蛋白gp120 线粒体功能障碍 过氧化物酶体增殖物激活受体γ辅助活化因子-1α 

分 类 号：R373.9[医药卫生—病原生物学]