减少晶状体中的氧化应激:提高晶状体中谷胱甘肽含量以预防白内障的替代措施。

IF 6 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Julie C Lim, Lanpeng Jiang, Natasha G Lust, Paul J Donaldson
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引用次数: 0

摘要

氧化应激在白内障的形成中起着重要作用,白内障是年龄增长、糖尿病或玻璃体切除手术后的结果。谷胱甘肽(GSH)是晶状体中的主要抗氧化剂,因此补充谷胱甘肽似乎是对抗晶状体氧化应激的直观策略。然而,向晶状体输送谷胱甘肽却困难重重,包括谷胱甘肽的快速降解导致其生物利用度有限、前眼球的解剖屏障导致谷胱甘肽无法充分输送到晶状体,以及晶状体内的细胞屏障限制了谷胱甘肽向不同区域的输送。因此,应更多地关注提高晶状体中 GSH 水平的替代方法。在本综述中,我们将重点讨论以下三种策略,它们利用晶状体的天然分子机制来提高其不同区域的 GSH 和/或抗氧化潜力:NRF2途径,该途径可调节参与GSH平衡的基因转录;使用脂质渗透性半胱氨酸类似物,以增加半胱氨酸用于GSH合成的可用性;以及上调晶状体内部微循环系统,该系统是Na+离子的循环电流,可驱动晶状体中的水运输,并随之推动半胱氨酸或GSH的潜在输送。前两种策略有可能恢复上皮和皮质中的 GSH 水平,而利用晶状体内部微循环系统的能力则有可能输送并提高晶状体核中的抗氧化剂水平。这是一个重要的区别,因为老年性白内障(核)和糖尿病性白内障(皮质)的损伤表型表明,抗氧化剂必须有针对性地输送到晶状体的不同区域,以减轻氧化应激。鉴于我们的老龄化和糖尿病人口不断增加,考虑如何利用晶状体的天然机制来恢复其不同区域的 GSH 水平并提供白内障保护变得越来越重要。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Minimizing Oxidative Stress in the Lens: Alternative Measures for Elevating Glutathione in the Lens to Protect against Cataract.

Oxidative stress plays a major role in the formation of the cataract that is the result of advancing age, diabetes or which follows vitrectomy surgery. Glutathione (GSH) is the principal antioxidant in the lens, and so supplementation with GSH would seem like an intuitive strategy to counteract oxidative stress there. However, the delivery of glutathione to the lens is fraught with difficulties, including the limited bioavailability of GSH caused by its rapid degradation, anatomical barriers of the anterior eye that result in insufficient delivery of GSH to the lens, and intracellular barriers within the lens that limit delivery of GSH to its different regions. Hence, more attention should be focused on alternative methods by which to enhance GSH levels in the lens. In this review, we focus on the following three strategies, which utilize the natural molecular machinery of the lens to enhance GSH and/or antioxidant potential in its different regions: the NRF2 pathway, which regulates the transcription of genes involved in GSH homeostasis; the use of lipid permeable cysteine-based analogues to increase the availability of cysteine for GSH synthesis; and the upregulation of the lens's internal microcirculation system, which is a circulating current of Na+ ions that drives water transport in the lens and with it the potential delivery of cysteine or GSH. The first two strategies have the potential to restore GSH levels in the epithelium and cortex, while the ability to harness the lens's internal microcirculation system offers the exciting potential to deliver and elevate antioxidant levels in its nucleus. This is an important distinction, as the damage phenotypes for age-related (nuclear) and diabetic (cortical) cataract indicate that antioxidant delivery must be targeted to different regions of the lens in order to alleviate oxidative stress. Given our increasing aging and diabetic populations it has become increasingly important to consider how the natural machinery of the lens can be utilized to restore GSH levels in its different regions and to afford protection from cataract.

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来源期刊
Antioxidants
Antioxidants Biochemistry, Genetics and Molecular Biology-Physiology
CiteScore
10.60
自引率
11.40%
发文量
2123
审稿时长
16.3 days
期刊介绍: Antioxidants (ISSN 2076-3921), provides an advanced forum for studies related to the science and technology of antioxidants. It publishes research papers, reviews and communications. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced. Electronic files and software regarding the full details of the calculation or experimental procedure, if unable to be published in a normal way, can be deposited as supplementary electronic material.
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