Light-evoked S-nitrosylation in the retina.
Light-evoked S-nitrosylation in the retina.
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DOI：
10.1002/cne.23780
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发表时间：
2015-10-01
期刊：
影响因子：
--
通讯作者：
Vigh J
中科院分区：
文献类型：
--
作者：
Tooker RE;Vigh J
视网膜中的一氧化氮（NO）合成由光刺激触发。已经显示NO通过激活NO信号传导的最敏感的靶标可溶性鸟苷酸环化酶来调节脊椎动物视网膜中多个位点的视觉信号处理。NO还可以改变蛋白质的结构和功能，并通过在称为S-亚硝基化的化学反应中与半胱氨酸残基的游离巯基结合而直接发挥生物学效应。然而，在包括视网膜在内的中枢神经系统中，这种反应在生理条件下并不显著。在这里，我们提供了广泛的S-亚硝基化，发生在金鱼和小鼠视网膜的生理相关的光强度下，在强度依赖性的方式，在两个物种具有惊人的相似模式的免疫组织化学证据。NEM，封闭S-亚硝基化，或与TRIM，神经元NO合酶的抑制剂预处理，消除了光诱发的S-亚硝基化蛋白免疫荧光（SNI）在两个物种的视网膜增加。同样，在缺乏神经元型NO合酶的转基因小鼠视网膜中，光并没有增加SNI，高于基础水平。用质谱法对光适应小鼠视网膜的定性分析揭示了300多种在光照下被S-亚硝基化的蛋白质，其中许多已知直接参与视网膜信号处理。我们的数据强烈表明，在视网膜中，光诱发的NO的产生导致广泛的S-亚硝基化，这一过程是一个重要的翻译后修饰影响广泛的蛋白质在生理条件下。
Nitric oxide (NO) synthesis in the retina is triggered by light stimulation. NO has been shown to modulate visual signal processing at multiple sites in the vertebrate retina, via activation of the most sensitive target of NO signaling, soluble guanylate cyclase. NO can also alter protein structure and function and exert biological effects directly by binding to free thiol groups of cysteine residues in a chemical reaction called S-nitrosylation. However, in the central nervous system, including the retina, this reaction has not been considered to be significant under physiological conditions. Here we provide immunohistochemical evidence for extensive S-nitrosylation that takes place in the goldfish and mouse retinas under physiologically relevant light intensities, in an intensity-dependent manner, with a strikingly similar pattern in both species. Pre-treatment with NEM, which occludes S-nitrosylation, or with TRIM, an inhibitor of neuronal NO synthase, eliminated the light-evoked increase in S-nitrosylated protein immunofluorescence (SNI) in the retinas of both species. Similarly, light did not increase SNI, above basal levels, in retinas of transgenic mice lacking neuronal NO synthase. Qualitative analysis of the light-adapted mouse retina with mass spectrometry revealed more than 300 proteins that were S-nitrosylated upon illumination, many of which are known to participate directly in retinal signal processing. Our data strongly suggest that in the retina, light-evoked NO production leads to extensive S-nitrosylation and that this process is a significant post-translational modification affecting a wide range of proteins under physiological conditions.
影响因子：
4.8
作者：
Rossi-George, Alba;Gow, Andrew J.
通讯作者：
Gow, Andrew J.