The glutathione system and its regulation by neurohormone melatonin in the central nervous system.
The glutathione system and its regulation by neurohormone melatonin in the central nervous system.
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DOI：
10.2174/187152410793429683
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发表时间：
2010-11
影响因子：
--
通讯作者：
J. Limón-Pacheco;M. Gonsebatt
中科院分区：
文献类型：
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作者：
J. Limón-Pacheco;M. Gonsebatt
谷胱甘肽系统包括谷胱甘肽的还原（GSH）和氧化（GSSG）形式;其合成和再循环所需的酶，如γ-谷氨酸半胱氨酸连接酶（γ-GCL）、谷胱甘肽合成酶（GS）、谷胱甘肽还原酶（GSR）和γ-谷氨酰转肽酶（γ-GGT）;以及其用于代谢和防御自由基诱导的氧化损伤的机制所需的酶，如谷胱甘肽S-转移酶（GST）和谷胱甘肽过氧化物酶（GPx）。谷氨酸在中枢神经系统（CNS）中的功能包括维持神经递质、膜保护、解毒、代谢调节和信号转导调节。在各种神经退行性疾病，如肌萎缩性侧索硬化症和阿尔茨海默病和帕金森病中的常见病理学标志是氧化应激的增加和抗氧化系统的失效，如GSH含量的降低。药理学剂量的外源性神经激素褪黑激素不仅能有效清除活性氧和氮，还能提高GSH水平以及GSH相关酶（包括γ-GCL、GPxs和GSR）的表达和活性。褪黑激素调节谷胱甘肽系统的确切机制尚未完全了解。这篇简短的综述的主要目的是讨论有关谷胱甘肽系统和褪黑激素在中枢神经系统中的潜在共同调制信号的证据。本文还讨论了神经元和非神经元细胞之间的相互作用及其可能的调控机制。
The glutathione system includes reduced (GSH) and oxidized (GSSG) forms of glutathione; the enzymes required for its synthesis and recycling, such as gamma-glutamate cysteine ligase (γ-GCL), glutathione synthetase (GS), glutathione reductase (GSR) and gamma glutamyl transpeptidase (γ-GGT); and the enzymes required for its use in metabolism and in mechanisms of defense against free radical-induced oxidative damage, such as glutathione s-transferases (GSTs) and glutathione peroxidases (GPxs). Glutathione functions in the central nervous system (CNS) include maintenance of neurotransmitters, membrane protection, detoxification, metabolic regulation, and modulation of signal transduction. A common pathological hallmark in various neurodegenerative disorders, such as amyotrophic lateral sclerosis and Alzheimer's and Parkinson's diseases is the increase in oxidative stress and the failure of antioxidant systems, such as the decrease in the GSH content. The administration of exogenous neurohormone melatonin at pharmacological doses has been shown not only to be an effective scavenger of reactive oxygen and nitrogen species but also to enhance the levels of GSH and the expression and activities of the GSH-related enzymes including γ-GCL, GPxs, and GSR. The exact mechanisms by which melatonin regulates the glutathione system are not fully understood. The main purpose of this short review is to discuss evidence relating to the potential common modulation signals between the glutathione system and melatonin in the CNS. The potential regulatory mechanisms and interactions between neurons and non-neuronal cells are also discussed.