Increased expression of glutathione peroxidase 4 strongly protects retina from oxidative damage.
Increased expression of glutathione peroxidase 4 strongly protects retina from oxidative damage.
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DOI：
10.1089/ars.2008.2171
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发表时间：
2009-04
影响因子：
6.6
通讯作者：
Campochiaro PA
中科院分区：
文献类型：
--
作者：
Lu L;Oveson BC;Jo YJ;Lauer TW;Usui S;Komeima K;Xie B;Campochiaro PA
氧化损伤导致视网膜色素变性中的视锥细胞死亡和年龄相关性黄斑变性中的视杆细胞、视锥细胞和视网膜色素上皮（RPE）细胞的死亡。在这项研究中，我们探讨了过表达内源性抗氧化防御系统的组成部分，以对抗RPE细胞和视网膜的氧化损伤的策略。在转染培养的RPE细胞中，超氧化物歧化酶1（SOD1）或SOD2的表达增加，有增加的组成性和应激诱导的氧化损伤的羰基加合物蛋白质的水平测量。相反，谷胱甘肽过氧化物酶1（Gpx1）或Gpx4表达增加的RPE细胞没有表现出组成性氧化损伤的增加。增加Gpx4，并在较小程度上Gpx1，减少氧化应激诱导的RPE细胞损伤。Gpx 4与SOD 1或2的共表达部分逆转了SOD的有害影响。产生了在光感受器中具有Gpx4诱导表达的转基因小鼠，并且在3种氧化损伤诱导的视网膜变性模型中，Gpx4表达的增加提供了对视网膜结构和功能的强保护。这些数据表明，在视网膜色素变性或年龄相关性黄斑变性患者中，应考虑采用基因治疗方法来增强视网膜和RPE中Gpx4的活性。
Oxidative damage contributes to cone cell death in retinitis pigmentosa and death of rods, cones, and retinal pigmented epithelial (RPE) cells in age-related macular degeneration. In this study, we explored the strategy of over-expressing components of the endogenous antioxidant defense system to combat oxidative damage in RPE cells and retina. In transfected cultured RPE cells with increased expression of superoxide dismutase1 (SOD1) or SOD2 there was increased constitutive and stress-induced oxidative damage measured by the level of carbonyl adducts on proteins. In contrast, RPE cells with increased expression of glutathione peroxidase 1 (Gpx1) or Gpx4 did not show an increase in constitutive oxidative damage. An increase in Gpx4, and to a lesser extent Gpx1, reduced oxidative stress-induced RPE cell damage. Co-expression of Gpx4 with SOD1 or 2 partially reversed the deleterious effects of the SODs. Transgenic mice with inducible expression of Gpx4 in photoreceptors were generated and in 3 models of oxidative damage-induced retinal degeneration, increased expression of Gpx4 provided strong protection of retinal structure and function. These data suggest that gene therapy approaches to augment the activity of Gpx4 in the retina and RPE should be considered in patients with retinitis pigmentosa or age-related macular degeneration.
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影响因子：
5.6
作者：
Komeima, Keiichi;Rogers, Brian S.;Campochiaro, Peter A.
通讯作者：
Campochiaro, Peter A.
影响因子：
--
作者：
Kassoff, A;Kassoff, J;Chew, EY
通讯作者：
Chew, EY
影响因子：
7.4
作者：
Buss, H;Chan, TP;Winterbourn, CC
通讯作者：
Winterbourn, CC
影响因子：
7.4
作者：
Cingolani, C;Rogers, B;Campochiaro, PA
通讯作者：
Campochiaro, PA
影响因子：
5.6
作者：
Dong, Aling;Shen, Jikui;Campochiaro, Peter A.
通讯作者：
Campochiaro, Peter A.