Extracellular Vesicles Mediate Anti-Oxidative Response-In Vitro Study in the Ocular Drainage System.
Extracellular Vesicles Mediate Anti-Oxidative Response-In Vitro Study in the Ocular Drainage System.
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DOI：
10.3390/ijms21176105
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发表时间：
2020-08-25
影响因子：
5.6
通讯作者：
Beit-Yannai E
中科院分区：
文献类型：
--
作者：
Lerner N;Chen I;Schreiber-Avissar S;Beit-Yannai E
细胞外囊泡（EV）作为信号传导介质的重要性在多种途径中得到了强调，但关于其在氧化应激（OS）期间作为保护性信息的作用的数据有限。眼部引流系统的独特之处在于，它持续暴露于 OS，并且携带 EV 的房水单向流动，在青光眼疾病中发挥作用。在这里，我们的目的是检查来自非色素性睫状上皮（NPCE）（暴露于 OS 的房水产生细胞）的 EV 向小梁网（TM）（房水排出细胞）传递保护信息的能力，这一过程对青光眼疾病的病理生理学具有重要意义。从暴露于非致死 OS 的 NPCE 细胞培养基中提取的 EV 及其无应激对照与 TM 细胞一起孵育。评估了源自氧化应激细胞的 EV 对核因子红细胞 2 相关因子 2-Kelch 样 ECH 相关蛋白 1 (Nrf2-Keap1)（一种主要 OS 通路）和 Wnt 通路（以其在原发性开角型青光眼中的作用而闻名）激活的影响。来自氧化 NPCE 细胞的 EV 显着保护 TM 细胞免受直接 OS 的影响。暴露后 8 小时，TM 细胞从氧化的 NPCE 中摄取 EV 及其胞质 Nrf2 水平显着升高。通过 qRT-PCR 测量，源自氧化 NPCE 细胞的 EV 显着减弱 TM 细胞中的 Wnt 蛋白表达，并激活主要抗氧化基因。暴露于源自氧化NPCE细胞的EV的TM细胞表现出显着较低的OS和较高的超氧化物歧化酶和过氧化氢酶活性。最后，我们能够证明，羰基化蛋白质和氧化蛋白质产物在氧化 NPCE 细胞衍生的 EV 中以显着更高的水平存在，支持了它们在信号传导过程中的作用。我们假设这些发现的意义可能超出了对青光眼疾病病理生理学的理解，并且传输激活靶细胞中抗氧化系统的信号代表了许多组织通讯中常见的广泛反应。
The importance of extracellular vesicles (EVs) as signaling mediators has been emphasized for several pathways with only limited data regarding their role as protective messages during oxidative stress (OS). The ocular drainage system is unique by being continuously exposed to OS and having a one-way flow of the aqueous humor carrying EVs taking role in glaucoma disease. Here, we aimed to examine the ability of EVs derived from the non-pigmented ciliary epithelium (NPCE)—the aqueous humor producing cells exposed to OS—to deliver protecting messages to the trabecular meshwork (TM)—the aqueous humor draining cells—a process with significance to the pathophysiology of glaucoma disease. EVs extracted from media of NPCE cells exposed to non-lethal OS and their unstressed control were incubated with TM cells. The effects of EVs derived from oxidative stressed cells on the activation of the nuclear factor erythroid 2-related factor 2-Kelch-like ECH-associated protein 1 (Nrf2-Keap1), a major OS pathway, and of the Wnt pathway, known for its role in primary open-angle glaucoma, were evaluated. EVs derived from oxidized NPCE cells significantly protected TM cells from direct OS. The TM cells uptake of EVs from oxidized NPCE and their cytosolic Nrf2 levels were significantly higher at 8 h post-exposure. EVs derived from oxidized NPCE cells significantly attenuated Wnt protein expression in TM cells and activated major antioxidant genes as measured by qRT-PCR. TM cells exposed to EVs derived from oxidized NPCE cells exhibited significantly lower OS and higher super oxide dismutase and catalase activity. Finally, we were able to show that carbonylated proteins and products of oxidized protein are presented in significantly higher levels in EVs derived from oxidized NPCE cells, supporting their suggested role in the signaling process. We hypothesize that these findings may have implications beyond understanding the pathophysiology of glaucoma disease and that transmitting signals that activate the antioxidant system in target cells represent a broad response common to many tissues communication.
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影响因子：
3.7
作者：
Lerner N;Beit-Yannai E
通讯作者：
Beit-Yannai E
影响因子：
16
作者：
Ludwig AK;De Miroschedji K;Doeppner TR;Börger V;Ruesing J;Rebmann V;Durst S;Jansen S;Bremer M;Behrmann E;Singer BB;Jastrow H;Kuhlmann JD;El Magraoui F;Meyer HE;Hermann DM;Opalka B;Raunser S;Epple M;Horn PA;Giebel B
通讯作者：
Giebel B
外泌体在氧化应激期间传达保护性信息；外泌体穿梭RNA的可能作用。
影响因子：
3.7
作者：
Eldh M;Ekström K;Valadi H;Sjöstrand M;Olsson B;Jernås M;Lötvall J
通讯作者：
Lötvall J
NRF2：氧化应激中的INRF2（KEAP1）信号传导。
影响因子：
7.4
作者：
Kaspar, James W.;Niture, Suryakant K.;Jaiswal, Anil K.
通讯作者：
Jaiswal, Anil K.
DOI：
10.2147/opth.s32933
发表时间：
2012
期刊：
Clinical ophthalmology (Auckland, N.Z.)
影响因子：
--
作者：
Beidoe G;Mousa SA
通讯作者：
Mousa SA