Methionine sulfoxide reductase A is important for lens cell viability and resistance to oxidative stress
Methionine sulfoxide reductase A is important for lens cell viability and resistance to oxidative stress
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DOI：
10.1073/pnas.0403532101
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发表时间：
2004-06-29
影响因子：
11.1
通讯作者：
Hejtmancik, JF
中科院分区：
文献类型：
--
作者：
Kantorow, M;Hawse, JR;Hejtmancik, JF
老年性白内障是一种眼晶状体混浊，是老年人视力受损的主要原因，其病因与氧化应激损伤有关。蛋氨酸氧化为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%，但基本上不存在于透明晶状体中。蛋氨酸氧化导致蛋白质功能的丧失，这种功能可以通过蛋氨酸亚砜还原酶A(MSRA)的作用而逆转，蛋氨酸亚硫氧化物还原酶A参与氧化应激保护，是从大肠杆菌到小鼠等物种长寿的重要调节因素。为了确定MSRA在晶状体氧化应激保护中的作用，我们检测了MSRA在人类晶状体中的水平和空间表达模式，并测试了MSRA直接保护晶状体细胞免受氧化应激的能力。在本报告中，我们证实MSRA存在于整个人类晶状体中，在那里它可能保护晶状体细胞及其成分免受蛋氨酸氧化。我们证明，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加敏感。我们还提供了证据表明，在没有外源应激的情况下，MSRA对于晶状体细胞的功能是重要的。总而言之，这些数据暗示MSRA在晶状体细胞活性和对氧化应激的抵抗力中起关键作用，氧化应激是老年性白内障病因中的一个主要因素。
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.