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首页> 外文期刊>Journal of cellular physiology. >The Nrf2 activator MIND4-17 protects retinal ganglion cells from high glucose-induced oxidative injury
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The Nrf2 activator MIND4-17 protects retinal ganglion cells from high glucose-induced oxidative injury

机译:Nrf2活化剂MIND4-17保护视网膜从高glucose-induced神经节细胞氧化损伤

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Diabetic retinopathy (DR) is a leading cause of acquired blindness among adults. High glucose (HG) induces oxidative injury and apoptosis in retinal ganglion cells (RGCs), serving as a primary pathological mechanism of DR. MIND4-17 activates nuclear-factor-E2-related factor 2 (Nrf2) signaling via modifying one cysteine (C151) residue of Kelch-like ECH-associated protein 1 (Keapl). The current study tested its effect in HG-treated primary murine RGCs. We show that MIND4-17 disrupted Keapl-Nrf2 association, leading to Nrf2 protein stabilization and nuclear translo-cation, causing subsequent expression of key Nrf2 target genes, including heme oxygenase-1 and NAD(P)H quinone oxidoreductase 1. Functional studies showed that MIND4-17 pretreatment significantly inhibited HG-induced cytotoxicity and apoptosis in primary murine RGCs. Reactive oxygen species production and oxidative injury in HG-treated murine RGCs were attenuated by MIND4-17. Nrf2 silencing (by targeted small interfering RNA) or knockout (by CRISPR/Cas9 method) abolished MIND4-17-induced RGC cytoprotection against HG. Additionally, Keapl knockout or silencing mimicked and abolished MIND4-17-induced activity in RGCs. In vivo, MIND4-17 intravitreal injection activated Nrf2 signaling and attenuated retinal dysfunction by light damage in mice. We conclude that MIND4-17 activates Nrf2 signaling to protect murine RGCs from HG-induced oxidative injury.
机译:糖尿病性视网膜病变(DR)的一个主要原因获得了成年人失明。(HG)诱导氧化损伤和细胞凋亡视网膜神经节细胞(RGCs)担任MIND4-17博士的主要病理机制激活nuclear-factor-E2-related因子2通过修改一个半胱氨酸(Nrf2)信号(C151)残留Kelch-like ECH-associated蛋白1 (Keapl)。在初选HG-treated小鼠RGCs效果。MIND4-17中断Keapl-Nrf2协会,导致Nrf2蛋白质稳定和核translo-cation,导致后续的表达关键Nrf2目标基因,包括血红素oxygenase-1和NAD (P) H醌氧化还原酶1。研究表明,MIND4-17预处理显著抑制HG-induced细胞毒性和细胞凋亡主要小鼠RGCs。氧物种生产和氧化损伤HG-treated鼠RGCs减毒了MIND4-17。由CRISPR干扰RNA)或淘汰赛(/ Cas9方法)废除MIND4-17-induced RGC对HG cytoprotection。此外,Keapl基因敲除或沉默模仿和废除在RGCs MIND4-17-induced活动。Nrf2 MIND4-17 intravitreal注入激活信号和减毒视网膜功能障碍光损伤的老鼠。保护小鼠RGCs激活Nrf2信号从HG-induced氧化损伤。

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