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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Methionine sulfoxide reductase A is important for lens cell viability and resistance to oxidative stress.
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Methionine sulfoxide reductase A is important for lens cell viability and resistance to oxidative stress.

机译：蛋氨酸亚砜还原酶A对于晶状体细胞生存力和抗氧化应激能力很重要。

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摘要

Age-related cataract, an opacity of the eye lens, is the leading cause of visual impairment in the elderly, the etiology of which is related to oxidative stress damage. Oxidation of methionine to methionine sulfoxide is a major oxidative stress product that reaches levels as high as 60% in cataract while being essentially absent from clear lenses. Methionine oxidation results in loss of protein function that can be reversed through the action of methionine sulfoxide reductase A (MsrA), which is implicated in oxidative stress protection and is an essential regulator of longevity in species ranging from Escherichia coli to mice. To establish a role for MsrA in lens protection against oxidative stress, we have examined the levels and spatial expression patterns of MsrA in the human lens and have tested the ability of MsrA to protect lens cells directly against oxidative stress. In the present report, we establish that MsrA is present throughout the human lens, where it is likely to defend lens cells and their components against methionine oxidation. We demonstrate that overexpression of MsrA protects lens cells against oxidative stress damage, whereas silencing of the MsrA gene renders lens cells more sensitive to oxidative stress damage. We also provide evidence that MsrA is important for lens cell function in the absence of exogenous stress. Collectively, these data implicate MsrA as a key player in lens cell viability and resistance to oxidative stress, a major factor in the etiology of age-related cataract.
机译：与年龄有关的白内障，即晶状体的混浊，是老年人视觉障碍的主要原因，其病因与氧化应激损伤有关。蛋氨酸氧化成蛋氨酸亚砜是一种主要的氧化应激产物，在白内障中高达60％的水平，而透明镜片却基本不存在。蛋氨酸氧化导致蛋白质功能丧失，可通过蛋氨酸亚砜还原酶A（MsrA）的作用来逆转，这与氧化应激保护有关，是从大肠杆菌到小鼠等物种寿命的重要调节剂。为了建立MsrA在晶状体抵抗氧化应激的保护中的作用，我们检查了人晶状体中MsrA的水平和空间表达模式，并测试了MsrA防止晶状体细胞直接抵抗氧化应激的能力。在本报告中，我们确定MsrA存在于整个人晶状体中，在这里它很可能保护晶状体细胞及其成分免受蛋氨酸氧化。我们证明了MsrA的过表达保护晶状体细胞免受氧化应激损伤，而MsrA基因的沉默使晶状体细胞对氧化应激损伤更敏感。我们还提供了证据，表明MsrA在缺乏外源性应激时对于晶状体细胞功能很重要。总的来说，这些数据暗示MsrA是晶状体细胞生存力和抗氧化应激的关键因素，而氧化应激是年龄相关性白内障病因的主要因素。

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