蛋白质O-GLcNAc糖基化与运动抗抑郁的神经机制  

Role of Protein O-Glc NAcylation in the Antidepressant Actions of Exercise

作　　者：王红梅[1,2] 刘微娜[1,2] 季浏[1,2] 

机构地区：[1]华东师范大学青少年健康评价与运动干预教育部重点实验室,上海200241 [2]华东师范大学体育与健康学院,上海200241

出　　处：《天津体育学院学报》2016年第2期125-130,共6页Journal of Tianjin University of Sport

基　　金：国家自然科学基金项目(项目编号:31200893);青少年POWER工程协同创新中心项目(项目编号:44801400);教育部重点实验室建设项目(项目编号:40500-541235-14203/004)

摘　　要：O-连接N-乙酰氨基葡萄糖转移酶(OGT)是蛋白质翻译后修饰过程中一个关键酶,主要分布于大脑、胰腺、胸腺以及人类的胎盘组织中,与OGA一起对细胞内1 000多种蛋白进行翻译后修饰,调节蛋白质的O-Glc NAc糖基化,进而调控细胞功能。OGT参与的糖基化修饰与胰岛素抵抗、糖尿病的并发症以及阿尔茨海默病关系密切。神经元形态复杂且局部能量需求大,突触部位能量供应特别依赖线粒体。在神经细胞内,OGT调节线粒体移动(motility),进而影响线粒体在神经元的分布,激活OGT,线粒体的能动性降低。OGT与其大部分底物的亲和力较低,但是与Milton蛋白的亲和力较高,并且可形成OGT-Milton复合体,OGT-Milton复合体能运送OGT穿过细胞膜,或绑定OGT移动到线粒体表面进行代谢调控。最近研究发现,靶向性敲除小鼠胎盘OGT,不仅线粒体的结构、代谢过程以及细胞的氧化还原状态等都受到影响,而且HPA轴活性、神经肽Y表达以及睾酮的合成也受到干扰,从而可导致抑郁行为。简要介绍OGT的结构与功能、OGT介导抑郁行为的关联机制,以及运动抗抑郁与O-Glc NAc糖基化调节之间的关系,旨在通过OGT阐明代谢紊乱与抑郁症之间的共病机制,为抑郁症的药物研发和运动干预提出新的发展方向。O-Linked N-acetylglucosamine transferase（OGT）,enriched in brain,pancreas,thymus and human placenta,plays an important role in the post-translational modification of proteins,mediating cellular metabolism and other functions. OGT is involved in insulin resistant,diabetes complications and Alzheimer disease through O-GlcNAcylation. An obvious site that requires mitochondria on neuronal processes is the synapse. In cultured primary cortical neurons,OGT regulates mitochondrial motility and distribution. Activated OGT can decrease mitochondrial activity. OGT has low-affinity interactions with many of its substrates but forms a stable complex with few. Milton was one of the first identified high-affinity OGT partners. OGT-dependent Milton O-GlcNAcylation links glucose metabolism to the regulation of mitochondrial motility. Recent studies indicated that a targeted placental disruption of OGT impaired mitochondrial structure,metabolic process and cell redox,as well as activity of HPA axis,expression of neuropeptide Y and testosterone production,thus led to depression.The current study aims to introduce the structure and function of OGT,the interventional mechanism of OGT in depression,and the role of protein O-GlcNAacylation in the antidepressant actions of exercise. The prospective findings may contribute to our understanding of the comorbidity between depression and metabolic diseases,and suggest a new target or guide for pharmacological research and exercise intervention against depression.

关 键 词：OGT 抑郁 运动 介导机制 

分 类 号：G804.5[文化科学—运动人体科学]