Targeting human 8-oxoguanine DNA glycosylase to mitochondria protects cells from high glucose-induced apoptosis
Targeting human 8-oxoguanine DNA glycosylase to mitochondria protects cells from high glucose-induced apoptosis
复制标题
将人 8-氧代鸟嘌呤 DNA 糖基化酶靶向线粒体可保护细胞免受高葡萄糖诱导的细胞凋亡
DOI：
10.1007/s12020-018-1575-7
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发表时间：
2018-03
期刊：
影响因子：
3.7
通讯作者：
Zhi-Peng You
中科院分区：
文献类型：
--
作者：
Yu-Ling Zou;Wen-Bin Luo;Lin Xie;Xin-Bang Mao;Chao Wu;Zhi-Peng You
目的糖尿病视网膜病变（diabetic retinopathy，DR）是一种主要由高糖引起的严重威胁视力的疾病.尽管做了很大的努力，探索DR的病因，其发病机制的确切机制仍然habitu.MethodsIn我们的研究中，我们通过链脲佐菌素（STZ）注射构建糖尿病大鼠。TUNEL法检测视网膜细胞凋亡。流式细胞仪检测线粒体膜电位（MMP）和活性氧（ROS）水平。结果与正常大鼠相比，糖尿病大鼠视网膜细胞凋亡率明显升高，线粒体呼吸链mRNA和蛋白表达水平明显降低。糖尿病大鼠8-OHdG信号增强，细胞色素C水平升高，MnSOD信号降低，NADPH-1水平降低。我们研究了高浓度葡萄糖下细胞靶向hOGG1（MTS-hOGG1）对原代rRECs的影响。与载体转染的细胞相比，MTS-hOGG1表达细胞可阻断高糖诱导的细胞凋亡、MMP的丢失和ROS的过度产生。另外，在高糖条件下，转染MTS-hOGG1可抑制细胞色素C的表达，但可促进细胞色素c氧化酶亚基1和NADPH-1的表达。结论高糖可通过引起MMP的丢失、ROS的过度产生和线粒体DNA的损伤而诱导细胞凋亡。靶向线粒体中的DNA修复酶hOGG1部分减轻了高糖诱导的后果，这为DR治疗提供了新的思路。
PurposeDiabetic retinopathy (DR) is a major vision threatening disease mainly induced by high glucose. Despite great efforts were made to explore the etiology of DR, the exact mechanism responsible for its pathogenesis remains elusive.MethodsIn our study, we constructed diabetic rats via Streptozotocin (STZ) injection. TUNEL assay was employed to examine retinal cell apoptosis. The levels of mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) were analyzed via flow cytometry. The mRNA and protein levels of mitochondrial respiratory chain were investigated by RT-qPCR and western blot.ResultsCompared with normal rats, the retinal cell apoptosis rate in diabetic rats was significantly upregulated. What’s more, the signals of 8-OHdG and the levels of Cytochrome C in diabetic rats were enhanced; however, the MnSOD signals and NADPH-1 levels were reduced. We investigated the effect of mitochondrialy targeted hOGG1 (MTS-hOGG1) on the primary rRECs under high glucose. Compared with vector-transfected cells, MTS-hOGG1-expressing cells blocked high glucose-induced cell apoptosis, the loss of MMP and the overproduction of ROS. In addition, under high glucose, MTS-hOGG1 transfection blocked the expression of Cytochrome C, but enhanced the expression of cytochrome c oxidase subunit 1 and NADPH-1.ConclusionsThese findings indicated that high glucose induced cell apoptosis by causing the loss of MMP, the overproduction of ROS and mtDNA damage. Targeting DNA repair enzymes hOGG1 in mitochondria partly mitigated the high glucose-induced consequences, which shed new light for DR therapy.
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影响因子：
2.4
作者：
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