Hydrogen peroxide causes significant mitochondrial DNA damage in human RPE cells
Hydrogen peroxide causes significant mitochondrial DNA damage in human RPE cells
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DOI：
10.1006/exer.1998.0661
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发表时间：
1999-06-01
影响因子：
3.4
通讯作者：
Godley, BF
中科院分区：
文献类型：
--
作者：
Ballinger, SW;Van Houten, B;Godley, BF
活性氧中间体介导的视网膜色素上皮细胞功能障碍被认为是老年性黄斑变性的可能原因。为了验证视网膜色素细胞易受活性氧中间体介导的遗传损伤的假设，我们在体外用50 μ M ~ 200 μ M的过氧化氢处理视网膜色素上皮细胞。使用定量聚合酶链反应评估线粒体DNA和三个核位点的损伤。过氧化氢处理视网膜色素上皮细胞导致线粒体DNA损伤显著增加。明显的线粒体DNA损伤发生迅速，治疗后3小时内未完全修复。相比之下，在三个不同的核位点（β -珠蛋白基因簇、hprt和β -聚合酶基因）中未观察到DNA损伤。与对照组相比，过氧化氢处理视网膜色素上皮细胞也导致线粒体氧化还原功能下降，与线粒体DNA损伤增加一致。因此，视网膜色素上皮细胞线粒体DNA在体外易受过氧化氢介导的损伤，因此，可能在导致视网膜色素上皮细胞功能障碍的初始事件中起催化剂作用。(C) 1999学术出版社。
Retinal pigment epithelial cell dysfunction mediated by reactive oxygen intermediates has been suggested as a possible cause of age-related macular degeneration. To test the hypothesis that retinal pigment cells are susceptible to genetic damage mediated by reactive oxygen intermediates, retinal pigment epithelial cells were treated with 50 mu M-200 mu M of hydrogen peroxide in vitro. Damage to mitochondrial DNA and three nuclear loci were assessed using quantitative polymerase chain reaction. Hydrogen peroxide treatment of retinal pigment epithelial cells resulted in significantly increased mitochondrial DNA damage. Significant mitochondrial DNA damage occurred rapidly and was not completely repaired within 3 hr post-treatment. By contrast, no DNA damage was observed in three different nuclear loci (beta-globin gene cluster, hprt, and beta-polymerase genes). Hydrogen peroxide treatment of retinal pigment epithelial cells also resulted in decreased mitochondrial redox function compared to controls, consistent with increased mitochondrial DNA damage. Consequently, retinal pigment epithelial cell mitochondrial DNA appears susceptible to hydrogen peroxide mediated damage in vitro, and thus, may serve as a catalyst in the initial events leading to retinal pigment epithelial cell dysfunction in vivo. (C) 1999 Academic Press.