Trotti D, Danbolt N C, Volterra A
Brigham and Women's Hospital, Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Trends Pharmacol Sci. 1998 Aug;19(8):328-34. doi: 10.1016/s0165-6147(98)01230-9.
Increasing evidence indicates that glutamate transporters are vulnerable to the action of biological oxidants, resulting in reduced uptake function. This effect could contribute to the build-up of neurotoxic extracellular glutamate levels, with major pathological consequences. Specific 'redox-sensing' elements, consisting of cysteine residues, have been identified in the structures of at least three transporter subtypes (GLT1, GLAST and EAAC1) and shown to regulate transport rate via thiol-disulphide redox interconversion. In this article, Davide Trotti, Niels Danbolt and Andrea Volterra discuss these findings in relation to the emerging view that in brain diseases oxidative and excitotoxic mechanisms might often operate in tight conjunction to induce neuronal damage. In particular, they review evidence suggesting a possible involvement of oxidative alterations of glutamate transporters in specific pathologies, including amyotrophic lateral sclerosis, Alzheimer's disease, brain trauma and ischaemia.
越来越多的证据表明，谷氨酸转运体易受生物氧化剂的作用影响，从而导致摄取功能降低。这种效应可能会促使具有神经毒性的细胞外谷氨酸水平升高，进而产生重大的病理后果。在至少三种转运体亚型（GLT1、GLAST和EAAC1）的结构中，已经鉴定出由半胱氨酸残基组成的特定“氧化还原感应”元件，这些元件通过硫醇-二硫键的氧化还原相互转化来调节转运速率。在本文中，达维德·特罗蒂、尼尔斯·丹博尔特和安德里亚·沃尔泰拉结合一种新出现的观点讨论了这些发现，该观点认为在脑部疾病中，氧化和兴奋性毒性机制可能经常紧密协同作用以诱导神经元损伤。特别是，他们回顾了相关证据，这些证据表明谷氨酸转运体的氧化改变可能参与特定的病理过程，包括肌萎缩侧索硬化症、阿尔茨海默病、脑外伤和缺血。
