Nitric oxide leads to cytoskeletal reorganization in the retinal pigment epithelium under oxidative stress.
Nitric oxide leads to cytoskeletal reorganization in the retinal pigment epithelium under oxidative stress.
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DOI：
10.4236/abb.2012.38143
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发表时间：
2012
期刊：
影响因子：
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通讯作者：
Jahng WJ
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文献类型：
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作者：
Sripathi SR;He W;Um JY;Moser T;Dehnbostel S;Kindt K;Goldman J;Frost MC;Jahng WJ
光是各种眼病的危险因素，包括年龄相关性黄斑变性（AMD）和视网膜色素变性（RP）。我们的目的是了解视网膜色素上皮（RPE）中的细胞骨架蛋白如何对氧化应激（包括光）做出反应，以及这些反应如何影响凋亡信号传导。先前，蛋白质组学分析显示，与视网膜退化1 （rd1）模型中12小时的光/暗循环暴露相比，连续光照7天的小鼠vimentin和丝氨酸/苏氨酸蛋白磷酸酶2A （PP2A）的表达水平显著增加。当动物在持续的光照下服用褪黑素时，vimentin和PP2A的水平会恢复到正常水平。Vimentin是PP2A的底物，它直接与Vimentin结合并使其去磷酸化。目前的研究表明，应激条件下PP2Ac（催化亚基）磷酸化上调与vimentin磷酸化呈负相关。波形蛋白的稳定似乎是通过一氧化氮诱导减少PP2Ac磷酸化来实现的。我们验证了我们的假设，即PP2Ac的位点特异性修饰可能通过一氧化氮信号通过波形蛋白去磷酸化驱动细胞骨架重组。我们推测一氧化氮决定了应激条件下蛋白质的硝化。我们的研究结果表明，PP2A和vimentin是由一氧化氮调节的，是参与细胞骨架信号传导的关键因素。目前的研究表明，外部应激增强一氧化氮调节PP2Ac和vimentin磷酸化，从而稳定或破坏vimentin。磷酸化可能导致波形蛋白解聚，导致非丝状颗粒的形成。我们认为，当细胞处于氧化应激时，稳定的vimentin可能作为抗凋亡分子。
Light is a risk factor for various eye diseases, including age-related macular degeneration (AMD) and retinitis pigmentosa (RP). We aim to understand how cytoskeletal proteins in the retinal pigment epithetlium (RPE) respond to oxidative stress, including light and how these responses affect apoptotic signaling. Previously, proteomic analysis revealed that the expression levels of vimentin and serine/threonine protein phosphatase 2A (PP2A) are significantly increased when mice are exposed under continuous light for 7 days compared to a condition of 12 hrs light/dark cycling exposure using retina degeneration 1 (rd1) model. When melatonin is administered to animals while they are exposed to continuous light, the levels of vimentin and PP2A return to a normal level. Vimentin is a substrate of PP2A that directly binds to vimentin and dephosphorylates it. The current study shows that upregulation of PP2Ac (catalytic subunit) phosphorylation negatively correlates with vimentin phosphorylation under stress condition. Stabilization of vimentin appears to be achieved by decreased PP2Ac phosphorylation by nitric oxide induction. We tested our hypothesis that site-specific modifications of PP2Ac may drive cytoskeletal reorganization by vimentin dephosphorylation through nitric oxide signaling. We speculate that nitric oxide determines protein nitration under stress conditions. Our results demonstrate that PP2A and vimentin are modulated by nitric oxide as a key element involved in cytoskeletal signaling. The current study suggests that external stress enhances nitric oxide to regulate PP2Ac and vimentin phosphorylation, thereby stabilizing or destabilizing vimentin. Phosphorylation may result in depolymerization of vimentin, leading to nonfilamentous particle formation. We propose that a stabilized vimentin might act as an anti-apoptotic molecule when cells are under oxidative stress.