Oxidative stress has been associated with the etipathogenesis of Diabetic retinopathy (DR). Studies have shown that DJ-1 plays an important role in regulating the reactive oxygen species (ROS) production and resistance to oxidative stress-induced apoptosis. This study aimed to investigate whether DJ-1 upregulates oxidative stress and prevents damage to retinal capillary pericytes by increasing antioxidant capacity through the Nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. Nrf2 is a redox-sensitive transcription factor that encode antioxidant enzymes and phase II metabolic enzymes, activation of Nrf2 functions is one of the critical defensive mechanisms against oxidative stress in many tissues. Our results showed after DJ-1 overexpression, apoptosis of rat retinal pericytes (RRPs) decreased, the ratio of B-cell lymphoma-2 (Bcl-2) to BCL2-Associated X Protein (BAX) increased, the production of ROS decreased, and the protein expression and activity of manganese superoxide dismutase (MnSOD, also called SOD2) and catalase (CAT) increased. DJ-1 overexpression activated Nrf2 expression, however, after Nrf2 silencing, apoptosis of RRPs increased, the ratio of Bcl-2 to BAX decreased, the production of ROS increased, the protein expression of MnSOD and CAT decreased, and the expression of heme oxygenase-1 (HO-1), NADP(H) quinone oxidoreductase (NQO1), glutamate-cysteine ligase catalytic subunit (GCLC) and modifier subunit (GCLM) decreased. These data suggest that enhancement of the Nrf2 pathway is a potential protective strategy for the treatment of DR. Therefore, DJ-1 may prevent high glucose-induced oxidative stress and RRPs apoptosis through the Nrf2 signaling pathway, thereby preventing the early onset and progression of DR.

译文

氧化应激与糖尿病性视网膜病(DR)的病因相关。研究表明,DJ-1在调节活性氧(ROS)的产生以及抵抗氧化应激诱导的细胞凋亡中起着重要作用。这项研究旨在调查DJ-1是否通过核因子红系2相关因子2(Nrf2)信号通路增加抗氧化能力,从而上调氧化应激并防止损害视网膜毛细血管周细胞。 Nrf2是氧化还原敏感的转录因子,编码抗氧化酶和II期代谢酶,Nrf2功能的激活是抵抗许多组织中氧化应激的关键防御机制之一。我们的结果显示,DJ-1过表达后,大鼠视网膜周细胞(RRP)的凋亡减少,B细胞淋巴瘤2(Bcl-2)与BCL2相关X蛋白(BAX)的比率增加,ROS的产生减少,锰超氧化物歧化酶(MnSOD,也称为SOD2)和过氧化氢酶(CAT)的蛋白质表达和活性增加。 DJ-1过表达激活了Nrf2的表达,但是,Nrf2沉默后,RRP的凋亡增加,Bcl-2与BAX的比例降低,ROS的产生增加,MnSOD和CAT的蛋白质表达降低,血红素加氧酶的表达-1(HO-1),NADP(H)醌氧化还原酶(NQO1),谷氨酸-半胱氨酸连接酶催化亚基(GCLC)和修饰子亚基(GCLM)降低。这些数据表明,Nrf2途径的增强是治疗DR的潜在保护策略。因此,DJ-1可能通过Nrf2信号传导途径阻止高葡萄糖诱导的氧化应激和RRPs凋亡,从而防止DR的早期发作和发展。

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