摘要
溶质载体家族1成员3(the solute carrier family 1 member 3 gene,SLC1A3)是一种重要的兴奋性氨基酸转运载体,在动物各组织器官中均有表达,主要负责细胞的酸性氨基酸转运,对动物健康与生长发育具有重要作用.目前关于SLC1A3的研究主要集中于对神经系统的调控以及表达异常造成的相关疾病,而对SLC1A3在其他组织器官中的研究较少.近期研究表明,SLC1A3可负责细胞内胞浆与线粒体之间的谷氨酸和天冬氨酸的转运,以维持线粒体内三羧酸循环和电子传递链的正常运转,促进细胞增殖,恢复细胞功能.本文主要综述了SLC1A3在动物各组织器官中的表达情况及其发挥的生物学功能,并解析了其对神经系统和线粒体功能的调控机制,以期SLC1A3作为关键靶点为调控动物机体健康和疾病治疗提供理论依据.
The solute carrier family 1 member 3(SLC1 A3) gene encodes for excitatory amino acid transporter 1(EAAT1), an important excitatory amino acid transporter. EAAT1 is mainly responsible for the transport of aspartate(Asp) and glutamate(Glu) in and out of the cell through the cell membrane, and plays an important role in regulating animal health and growth. To date, research on SLC1 A3 has mostly focused on its role in the nervous system and tumor tissues, whereas little is known about the regulation of SLC1 A3 in other systems and tissues.This paper reviews the expression, distribution, and biological function of SLC1 A3 in various animal tissues and organs.SLC1 A3 exhibits the highest expression in the nervous system of animals. It participates in excitatory conduction in the synaptic cleft by transporting the neurotransmitter Glu, thus maintaining the normal functioning of the nervous system and preventing damage to the nervous system caused by the neurotoxic effects of Glu. SLC1 A3 is also widely distributed in the digestive, circulatory, motor, endocrine, and reproductive systems and plays an important role in regulating mitochondrial function, cell proliferation, metabolism, nutrition, and immunity.We analyzed the gene regulatory mechanism of SLC1 A3 in the nervous system and mitochondria. In the nervous system,SLC1 A3 is expressed by astrocytes and maintains a low concentration of extracellular Glu by transporting Glu from the synaptic cleft into the cell, thereby preventing glutamate-induced excitotoxicity in the nervous system.Reduced expression and function of SLC1 A3 induce neurodegeneration in the brain matter, thus creating a space for cancer cells to survive. Additionally, SLC1 A3 is responsible for the intracellular transport of Glu and Asp between the cytoplasm and mitochondria, as well as maintenance of the normal operation of the tricarboxylic acid(TCA) cycle and mitochondrial electron transport chain(ETC) to promote cell proliferation and restore cellular function. For example,SLC1 A3 helps cancer cells to survive under nutrient-limiting conditions by transporting Asp under conditions of cellular glutamine starvation. SLC1 A3 ensures high uptake of Glu in the heart to maintain the normal state of electron acceptors and the TCA cycle, thereby promoting the functioning of cardiomyocytes and protecting the heart under hypoxic or ischemic conditions. In case of ETC inhibition, an insufficient supply of electron acceptors in the cells inhibits de novo glutamine biosynthesis. SLC1 A3 replaces the electron acceptor in the ETC, thereby transporting Asp and restoring the anabolism of Asp, which is beneficial for cell proliferation.Finally, SLC1 A3 is expressed in different tissues and cells and exhibits a potential regulatory effect on the growth and metabolism of the body. SLC1 A3 can be used as a transporter of acidic amino acids, and in the urea cycle, TCA cycle, and the malate/aspartate shuttle to provide nutrition, relieve oxidative stress, and enhance immunity. Therefore, extensive research and discussion on the functioning of acidic amino acid transporters such as SLC1 A3 can provide a theoretical basis using them as key targets for regulating animal health and improving disease treatment.
作者
丁婧
何流琴
李铁军
印遇龙
Jing Ding;Liuqin He;Tiejun Li;Yulong Yini(Hunan Provincial Key Laboratory of Animal Nutrition Physiology and Metabolism Process,Key Laboratoryof Agro-Ecological Proceses in Subtropical Region,Institute of Subtropical Agriculture,Chinese Academy of Sciences,Changsha 410125,China;Hunan Province Key Laboratory of Anima inesial Function and Regulation,College of ife Science,Hunan Normal University,Changsha 410081,China;Universiy of Chinese Academy of Sciences,Bejing 100049,China)
出处
《科学通报》
EI
CAS
CSCD
北大核心
2022年第25期3005-3013,共9页
Chinese Science Bulletin
基金
国家自然科学基金(31902168)
湖南省“湖湘青年英才”项目(2020RC3052)
湖南省重点研发项目(2022NK2023,2020NK2059)资助。
