Department of Ophthalmology, the second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China.
Hunan Clinical Research Center of Ophthalmic Disease, Changsha, Hunan, 410011, China.
Sci Rep. 2020 Feb 12;10(1):2477. doi: 10.1038/s41598-020-59408-2.
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.
氧化应激与糖尿病性视网膜病变 (DR) 的发病机制有关。研究表明，DJ-1 在调节活性氧 (ROS) 产生和抵抗氧化应激诱导的细胞凋亡方面发挥重要作用。本研究旨在探讨 DJ-1 是否通过核因子红细胞 2 相关因子 2 (Nrf2) 信号通路增加抗氧化能力来上调氧化应激并防止视网膜毛细血管周细胞损伤。Nrf2 是一种氧化还原敏感的转录因子，可编码抗氧化酶和 II 相代谢酶，激活 Nrf2 功能是许多组织中抵抗氧化应激的关键防御机制之一。我们的研究结果表明，DJ-1 过表达后，大鼠视网膜周细胞 (RRPs) 的凋亡减少，B 细胞淋巴瘤-2 (Bcl-2) 与 BCL2 相关 X 蛋白 (BAX) 的比值增加，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) 的蛋白表达和活性增加。DJ-1 过表达激活了 Nrf2 的表达，然而，在 Nrf2 沉默后，RRPs 的凋亡增加，Bcl-2 与 BAX 的比值降低，ROS 的产生增加，MnSOD 和 CAT 的蛋白表达减少，血红素加氧酶-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) 和修饰亚基 (GCLM) 的表达减少。这些数据表明，增强 Nrf2 通路是治疗 DR 的一种潜在保护策略。因此，DJ-1 可能通过 Nrf2 信号通路预防高糖诱导的氧化应激和 RRPs 凋亡，从而防止 DR 的早期发生和进展。
