High glucose (HG)-induced oxidative damage of retinal ganglion cells (RGCs) contributes to the pathogenesis of diabetic retinopathy, a severe complication of diabetes mellitus. Brahma-related gene 1 (Brg1) has currently emerged as a cytoprotective protein that alleviates oxidative damage induced by various stress. However, whether Brg1 is involved in the regulation of HG-induced oxidative damage of RGCs remains unknown. In this study, we aimed to investigate the potential role and underlying mechanism of Brg1 in regulating HG-induced damage of RGCs. We found that Brg1 expression was significantly downregulated in RGCs in response to HG treatment. Functional experiments showed that Brg1 knockdown enhanced HG-induced apoptosis and production of reactive oxygen species, while Brg1 overexpression suppressed HG-induced apoptosis and reactive oxygen species production, showing a protective effect. Moreover, Brg1 overexpression resulted in an increase in nuclear expression of nuclear factor-erythroid-2-related factor-2 (Nrf2) and the expression of heme oxygenase-1 (HO-1) in RGCs. Notably, inhibition of Nrf2 or HO-1 significantly blocked Brg1-mediated protection against HG-induced damage. Overall, these findings demonstrate that Brg1 protects RGCs from HG-induced oxidative damage through promotion of Nrf2/HO-1 signaling, indicating a potential role of Brg1 in the pathogenesis of diabetic retinopathy.

译文

:高葡萄糖(HG)诱导的视网膜神经节细胞(RGCs)氧化损伤导致糖尿病性视网膜病(糖尿病的一种严重并发症)的发病机理。梵天相关基因1(Brg1)目前已作为一种细胞保护蛋白出现,减轻了各种压力引起的氧化损伤。然而,Brg1是否参与HG诱导的RGC氧化损伤的调控尚不清楚。在这项研究中,我们旨在研究Brg1在调节HG诱导的RGC损伤中的潜在作用及其潜在机制。我们发现响应HG治疗,RGC中Brg1表达显着下调。功能实验表明,Brg1敲低增强了HG诱导的细胞凋亡和活性氧的产生,而Brg1过表达抑制了HG诱导的细胞凋亡和活性氧的产生,显示出保护作用。此外,Brg1的过表达导致RGCs中核因子-类胡萝卜素-2相关因子2(Nrf2)的核表达和血红素加氧酶-1(HO-1)的表达增加。值得注意的是,Nrf2或HO-1的抑制作用显着阻断了Brg1介导的针对HG诱导的损伤的保护作用。总体而言,这些发现表明Brg1通过促进Nrf2 / HO-1信号传导保护RGC免受HG诱导的氧化损伤,表明Brg1在糖尿病性视网膜病的发病机理中具有潜在的作用。

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