Oxidative damage of mitochondrial DNA in diabetes and its protection by manganese superoxide dismutase.
Oxidative damage of mitochondrial DNA in diabetes and its protection by manganese superoxide dismutase.
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DOI：
10.3109/10715760903494168
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发表时间：
2010-03
影响因子：
3.3
通讯作者：
Kowluru RA
中科院分区：
文献类型：
--
作者：
Madsen-Bouterse SA;Zhong Q;Mohammad G;Ho YS;Kowluru RA
糖尿病时视网膜线粒体功能紊乱，超氧阴离子自由基产生增加；MnSOD的过度表达消除了线粒体功能障碍，阻止了糖尿病视网膜病变的发展。线粒体DNA(MtDNA)特别容易受到氧化损伤。本研究的目的是研究MnSOD在线粒体DNA维持中的作用。观察MnSOD模拟、MnTBAP和MnSOD过表达对葡萄糖诱导的视网膜内皮细胞线粒体DNA动态平衡的影响及其功能后果。视网膜内皮细胞暴露在高糖环境中，线粒体DNA损伤增加，DNA修复机制受损。电子传递链复合体的线粒体编码蛋白基因表达降低。用MnTBAP或通过过量表达MnSOD抑制超氧阴离子自由基可防止线粒体DNA损伤并保护线粒体编码基因。因此，保护线粒体DNA免受葡萄糖诱导的氧化损伤是MnSOD改善糖尿病视网膜病变的可能机制之一。
Retinal mitochondria become dysfunctional in diabetes and the production of superoxide radicals is increased; over-expression of MnSOD abrogates mitochondrial dysfunction and prevents the development of diabetic retinopathy. The mitochondrial DNA (mtDNA) is particularly prone to oxidative damage. The aim of this study is to examine the role of MnSOD in the maintenance of mtDNA. The effect of MnSOD mimic, MnTBAP or over-expression of MnSOD on glucose-induced alterations in mtDNA homeostasis and its functional consequence was determined in retinal endothelial cells. Exposure of retinal endothelial cells to high glucose increased mtDNA damage and compromised the DNA repair machinery. The gene expressions of mitochondrial-encoded proteins of the electron transport chain complexes were decreased. Inhibition of superoxide radicals by either MnTBAP or by over-expression of MnSOD prevented mtDNA damage and protected mitochondrial-encoded genes. Thus, the protection of mtDNA from glucose-induced oxidative damage is one of the plausible mechanisms by which MnSOD ameliorates the development of diabetic retinopathy.
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影响因子：
4.4
作者：
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通讯作者：
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作者：
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通讯作者：
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