Overexpression of SOD in retina: need for increase in H2O2-detoxifying enzyme in same cellular compartment.
Overexpression of SOD in retina: need for increase in H2O2-detoxifying enzyme in same cellular compartment.
复制标题
视网膜中 SOD 过度表达：同一细胞区室中需要增加 H2O2 解毒酶。
DOI：
10.1016/j.freeradbiomed.2011.06.010
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发表时间：
2011
影响因子：
7.4
通讯作者：
Campochiaro,PeterA
中科院分区：
文献类型：
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作者：
Usui,Shinichi;Oveson,BrianC;Iwase,Takeshi;Lu,Lili;Lee,SunYoung;Jo,Young-Joon;Wu,Zhihao;Choi,Eun-Young;Samulski,RichardJ;Campochiaro,PeterA
在色素性视网膜炎（RP）中，各种突变导致视杆光感受器细胞死亡，导致视网膜外氧水平升高，视锥细胞进行性氧化损伤，视锥细胞功能逐渐丧失。我们一直在探索过表达内源性抗氧化防御系统成分的潜力，以保护rd10+/+小鼠（RP模型）的锥体细胞功能。与SOD1水平正常的rd10+/+小鼠相比，缺乏超氧化物歧化酶1 （SOD1）的rd10+/+小鼠视网膜中超氧化物自由基和羰基加合物（氧化损伤的标志）水平增加，锥体功能丧失更快。这表明SOD1是锥体抗氧化防御系统的重要组成部分，但在rd10+/+小鼠中，SOD1表达增加会增加氧化损伤，加速锥体功能的丧失。在rd10+/+小鼠中，SOD1与谷胱甘肽过氧化物酶4 （glutathione peroxidase 4, Gpx4）共表达，减少视网膜氧化损伤，显著减缓锥体细胞功能的丧失，Gpx4与SOD1一样定位于细胞质中，但不与过氧化氢酶靶向线粒体。基因转移导致SOD2表达增加，但SOD2与线粒体Gpx4不共表达，导致视网膜中h2o2水平升高。这些数据表明，为了在RP中提供益处，SOD的过表达必须与同一细胞室中过氧化物解毒酶的表达相结合。
In retinitis pigmentosa (RP), various mutations cause rod photoreceptor cell death leading to increased oxygen levels in the outer retina, progressive oxidative damage to cones, and gradual loss of cone cell function. We have been exploring the potential of overexpressing components of the endogenous antioxidant defense system to preserve cone cell function in rd10+/+mice, a model of RP. rd10+/+mice deficient in superoxide dismutase 1 (SOD1) showed increased levels of superoxide radicals and carbonyl adducts (a marker of oxidative damage) in the retina and more rapid loss of cone function than rd10+/+mice with normal levels of SOD1. This suggests that SOD1 is an important component of the antioxidant defense system of cones, but increased expression of SOD1 in rd10+/+mice increased oxidative damage and accelerated the loss of cone function. Coexpression of SOD1 with glutathione peroxidase 4 (Gpx4), which like SOD1 is localized in the cytoplasm, but not with catalase targeted to the mitochondria, reduced oxidative damage in the retina and significantly slowed the loss of cone cell function in rd10+/+mice. Gene transfer resulting in increased expression of SOD2, but not coexpression of SOD2 and mitochondrial Gpx4, resulted in high levels of H2O2in the retina. These data suggest that to provide benefit in RP, overexpression of an SOD must be combined with expression of a peroxide-detoxifying enzyme in the same cellular compartment.