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Identification, Expression, and Roles of the Cystine/Glutamate Antiporter in Ocular Tissues.
Oxidative Medicine and Cellular Longevity Pub Date : 2020-06-18 , DOI: 10.1155/2020/4594606
Renita M Martis 1, 2 , Luis J Knight 1, 2 , Paul J Donaldson 1, 2 , Julie C Lim 1, 2
Affiliation  

The cystine/glutamate antiporter (system xc-) is composed of a heavy chain subunit 4F2hc linked by a disulphide bond to a light chain xCT, which exchanges extracellular cystine, the disulphide form of the amino acid cysteine, for intracellular glutamate. In vitro research in the brain, kidney, and liver have shown this antiporter to play a role in minimising oxidative stress by providing a source of intracellular cysteine for the synthesis of the antioxidant glutathione. In vivo studies using the xCT knockout mouse revealed that the plasma cystine/cysteine redox couple was tilted to a more oxidative state demonstrating system xc- to also play a role in maintaining extracellular redox balance by driving a cystine/cysteine redox cycle. In addition, through import of cystine, system xc- also serves to export glutamate into the extracellular space which may influence neurotransmission and glutamate signalling in neural tissues. While changes to system xc- function has been linked to cancer and neurodegenerative disease, there is limited research on the roles of system xc- in the different tissues of the eye, and links between the antiporter, aging, and ocular disease. Hence, this review seeks to consolidate research on system xc- in the cornea, lens, retina, and ocular humours conducted across several species to shed light on the in vitro and in vivo roles of xCT in the eye and highlight the utility of the xCT knockout mouse as a tool to investigate the contribution of xCT to age-related ocular diseases.

中文翻译:

胱氨酸/谷氨酸逆转运蛋白在眼组织中的鉴定,表达和作用。

胱氨酸/谷氨酸反向转运蛋白(系统X Ç - )由重链亚单位4F2hc连接通过二硫键与轻链XCT,其中的交流胞外胱氨酸,氨基酸半胱氨酸的二硫键形式,胞内谷氨酸。脑,肾和肝中的体外研究表明,这种反转运蛋白通过提供细胞内半胱氨酸的来源来合成抗氧化剂谷胱甘肽,从而在最小化氧化应激中发挥作用。在体内使用XCT研究基因敲除小鼠显示,该等离子体胱氨酸/半胱氨酸的氧化还原对是倾斜至多种氧化状态展示系x Ç -通过驱动半胱氨酸/半胱氨酸氧化还原循环在维持细胞外氧化还原平衡中也起作用。此外,通过胱氨酸的进口,系x Ç -还用于出口谷氨酸成可在神经组织影响神经传递和谷氨酸盐发信号的细胞外空间。虽然系统X变化Ç -功能已经与癌症和神经退行性疾病,有X系统上的作用有限的研究Ç -在眼的不同组织和逆向转运蛋白之间的联系,老化,和眼部疾病。因此,本综述旨在巩固对系统x c的研究-跨多个物种进行的角膜,晶状体,视网膜和眼部幽默的研究,以阐明xCT在眼中的体外体内作用,并强调了xCT基因敲除小鼠作为研究xCT对与年龄有关的眼疾。
更新日期:2020-06-18
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