Ballatori Nazzareno, Krance Suzanne M, Notenboom Sylvia, Shi Shujie, Tieu Kim, Hammond Christine L
Department of Environmental Medicine, University of Rochester School of Medicine, Rochester, NY 14642, USA.
Biol Chem. 2009 Mar;390(3):191-214. doi: 10.1515/BC.2009.033.
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. Owing to the pleiotropic effects of GSH 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 acquired 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 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.
谷胱甘肽（GSH）在众多细胞过程中发挥着重要作用，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，这些疾病包括癌症、衰老相关疾病、囊性纤维化以及心血管、炎症、免疫、代谢和神经退行性疾病。由于 GSH 对细胞功能具有多效性作用，尽管正在取得重大进展，但要确定 GSH 在人类疾病的发生和/或表达中的作用一直相当困难。GSH 的水平、周转率和/或氧化状态可能会因参与其稳态的酶、转运蛋白、信号分子或转录因子的遗传或获得性缺陷，或因接触活性化学物质或代谢中间体而受到损害。GSH 缺乏或 GSH/谷胱甘肽二硫化物比率降低主要表现为对氧化应激的易感性增加，由此产生的损伤被认为与癌症、帕金森病和阿尔茨海默病等疾病有关。此外，GSH 水平的失衡会影响免疫系统功能，并被认为在衰老过程中起作用。正如细胞内低 GSH 水平会降低细胞抗氧化能力一样，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，这在许多癌细胞中都有观察到。一些肿瘤细胞中较高的 GSH 水平通常也与较高水平的 GSH 相关酶和转运蛋白有关。尽管这些变化的机制和影响尚未明确，但高 GSH 含量使癌细胞具有化学抗性，这是限制药物治疗的一个主要因素。本报告强调并整合了 GSH 稳态失衡与多种人类疾病之间日益增多的联系。
