Glutathione dysregulation and the etiology and progression of human diseases.
Glutathione dysregulation and the etiology and progression of human diseases.
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DOI：
10.1515/bc.2009.033
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发表时间：
2009-03
影响因子：
3.7
通讯作者：
Hammond CL
中科院分区：
文献类型：
--
作者：
Ballatori N;Krance SM;Notenboom S;Shi S;Tieu K;Hammond CL
谷胱甘肽（GSH）在许多细胞过程中起重要作用，包括细胞分化、增殖和凋亡，因此，GSH稳态的紊乱与许多人类疾病的病因和/或进展有关，包括癌症、衰老疾病、囊性纤维化和心血管、炎性、免疫、代谢和神经变性疾病。由于GSH对细胞功能的多效性作用，尽管正在取得重大进展，但很难确定GSH在人类疾病的发作和/或表达中的作用。GSH水平、周转率和/或氧化态可因参与其稳态的酶、转运蛋白、信号分子或转录因子的遗传或获得性缺陷或因暴露于反应性化学物质或代谢中间体而受损。GSH缺乏或GSH/谷胱甘肽二硫化物（GSSG）比率的降低主要通过增加对氧化应激的敏感性来表现，并且所产生的损害被认为与诸如癌症、帕金森病和阿尔茨海默病的疾病有关。此外，GSH水平的不平衡会影响免疫系统功能，并被认为在衰老过程中发挥作用。正如低细胞内GSH水平降低细胞的抗氧化能力，GSH水平升高通常会增加抗氧化能力和对氧化应激的抵抗力，这在许多癌细胞中观察到。某些肿瘤细胞中较高的GSH水平通常也与较高水平的GSH相关酶和转运蛋白相关。虽然这些变化的机制和意义都没有很好的定义，但高GSH含量使癌细胞具有化学抗性，这是限制药物治疗的主要因素。本报告强调并整合了GSH体内平衡失衡与多种人类疾病之间日益增长的联系。
Glutathione (GSH) plays an important role in a multitude of cellular processes, including cell differentiation, proliferation, and apoptosis, and as a result, disturbances in GSH homeostasis are implicated in the etiology and/or progression of a number of human diseases, including cancer, diseases of aging, cystic fibrosis, and cardiovascular, inflammatory, immune, metabolic, and neurodegenerative diseases. Because of GSH’s pleiotropic effects on cell functions, it has been quite difficult to define the role of GSH in the onset and/or the expression of human diseases, although significant progress is being made. GSH levels, turnover rates and/or oxidation state can be compromised by inherited or aquired defects in the enzymes, transporters, signaling molecules, or transcription factors that are involved in its homeostasis, or from exposure to reactive chemicals or metabolic intermediates. GSH deficiency or a decrease in the GSH/glutathione disulfide (GSSG) ratio manifests itself largely through an increased susceptibility to oxidative stress, and the resulting damage is thought to be involved in diseases such as cancer, Parkinson’s disease, and Alzheimer’s disease. In addition, imbalances in GSH levels affect immune system function, and are thought to play a role in the aging process. Just as low intracellular GSH levels decrease cellular antioxidant capacity, elevated GSH levels generally increase antioxidant capacity and resistance to oxidative stress, and this is observed in many cancer cells. The higher GSH levels in some tumor cells are also typically associated with higher levels of GSH-related enzymes and transporters. Although neither the mechanism nor the implications of these changes are well defined, the high GSH content makes cancer cells chemoresistant, which is a major factor that limits drug treatment. The present report highlights and integrates the growing connections between imbalances in GSH homeostasis and a multitude of human diseases.