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代谢和蛋白质分子水平上白内障发展研究中的非侵入性技术

Non-invasive techniques in the study of cataract development at the metabolic and protein molecular level.

作者信息

Garner W H

出版信息

Ciba Found Symp. 1984;106:248-65. doi: 10.1002/9780470720875.ch15.

DOI:10.1002/9780470720875.ch15
PMID:6568977
Abstract

Metabolic changes may precede changes in lens protein structure and cataract opacification. Since many of the effects associated with cataract are oxidative in nature, changes in the redox state may be caused by alterations in the level of various metabolic intermediates such as ATP and NAD(P)H. Abnormal levels of H2O2 have been found in the aqueous fluid of cataract patients. Lenses have been treated with 1 mM-H2O2 in organ culture as a cataract model. H2O2 in this system uncouples Na+, K+-ATPase. This metabolic stress has been further evaluated non-invasively by 31P NMR to show that H2O2 can reduce ATP levels without any immediate effects on visual transparency. However, further treatment by this oxidant leads to definitive visual changes in lens clarity. These changes may be due to further changes in structural lens proteins caused by denaturation and aggregation induced by H2O2. The effects of H2O2 on isolated lens proteins is being examined in molecular detail by NMR to ascertain how the lens proteins become denatured in solution. The relevance of the H2O2 model to cataract formation can only be evaluated by using several non-invasive techniques beyond NMR, and then critically comparing the model systems with human cataract tissue samples.

摘要

代谢变化可能先于晶状体蛋白质结构的变化和白内障的浑浊。由于许多与白内障相关的效应本质上是氧化性的,氧化还原状态的变化可能由各种代谢中间产物如ATP和NAD(P)H水平的改变引起。在白内障患者的房水中发现了异常水平的过氧化氢。在器官培养中用1 mM的过氧化氢处理晶状体作为白内障模型。该系统中的过氧化氢使钠钾ATP酶解偶联。这种代谢应激已通过31P核磁共振进行了非侵入性进一步评估,结果表明过氧化氢可降低ATP水平,且对视觉透明度无任何即时影响。然而,这种氧化剂的进一步处理会导致晶状体透明度出现明确的视觉变化。这些变化可能是由于过氧化氢诱导的变性和聚集导致晶状体结构蛋白进一步变化所致。正通过核磁共振从分子层面详细研究过氧化氢对分离的晶状体蛋白的影响,以确定晶状体蛋白在溶液中是如何变性的。只有通过使用除核磁共振之外的几种非侵入性技术,然后严格地将模型系统与人类白内障组织样本进行比较,才能评估过氧化氢模型与白内障形成的相关性。

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