The Role of Reactive Oxygen and Nitrogen Species in the Expression and Splicing of Nitric Oxide Receptor.
The Role of Reactive Oxygen and Nitrogen Species in the Expression and Splicing of Nitric Oxide Receptor.
复制标题
活性氧和氮在一氧化氮受体表达和剪接中的作用。
DOI：
10.1089/ars.2016.6687
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发表时间：
2017
影响因子：
6.6
通讯作者：
Martin,Emil
中科院分区：
文献类型：
--
作者：
Sharina,IraidaG;Martin,Emil
意义：一氧化氮 (NO) 依赖性信号传导对于许多细胞功能和生理过程至关重要。可溶性鸟苷酸环化酶 (sGC) 作为 NO 受体并介导大部分 NO 功能。 NO 和 sGC 之间的信号传导受到活性氧和氮物种的强烈改变。最新进展：除了 NO 清除之外，sGC 还受到 sGC 血红素氧化/丢失、半胱氨酸残基氧化或亚硝化以及磷酸化的影响。 Apo-sGC 或含有氧化血红素的 sGC 是降解的目标。 sGC 转录和 sGC mRNA 的稳定性也受到氧化应激的影响。关键问题：本综述引用的研究表明，在短期或中度氧化应激条件下，存在使细胞过程适应 sGC 功能减弱的补偿过程。 sGC 转录本的选择性剪接被认为是一种可能增强和减少 sGC 功能的机制。 α1 同工型 B（人 α1 sGC 亚基的功能性且稳定的剪接变体）的表达被认为是此类补偿机制之一。功能失调的剪接异构体的表达被认为是血管疾病中 sGC 功能下降的一个因素。未来方向：针对 sGC 剪接过程可能是维持正常条件下健康组织中表达的 sGC 转录本组成的重要方法。新兴的新策略允许对 RNA 剪接进行有针对性的操作，这为使用这种方法作为预防措施和控制 sGC 剪接异构体的组成提供了机会。表达的 sGC 剪接形式的合理管理可能是现有 sGC 导向疗法的有价值的补充治疗策略。氧化还原信号。 26、122-136。
Significance:Nitric oxide (NO)-dependent signaling is critical to many cellular functions and physiological processes. Soluble guanylyl cyclase (sGC) acts as an NO receptor and mediates the majority of NO functions. The signaling between NO and sGC is strongly altered by reactive oxygen and nitrogen species.Recent Advances:Besides NO scavenging, sGC is affected by oxidation/loss of sGC heme, oxidation, or nitrosation of cysteine residues and phosphorylation. Apo-sGC or sGC containing oxidized heme is targeted for degradation. sGC transcription and the stability of sGC mRNA are also affected by oxidative stress.Critical Issues:Studies cited in this review suggest the existence of compensatory processes that adapt cellular processes to diminished sGC function under conditions of short-term or moderate oxidative stress. Alternative splicing of sGC transcripts is discussed as a mechanism with the potential to both enhance and reduce sGC function. The expression of α1 isoform B, a functional and stable splice variant of human α1 sGC subunit, is proposed as one of such compensatory mechanisms. The expression of dysfunctional splice isoforms is discussed as a contributor to decreased sGC function in vascular disease.Future Directions:Targeting the process of sGC splicing may be an important approach to maintain the composition of sGC transcripts that are expressed in healthy tissues under normal conditions. Emerging new strategies that allow for targeted manipulations of RNA splicing offer opportunities to use this approach as a preventive measure and to control the composition of sGC splice isoforms. Rational management of expressed sGC splice forms may be a valuable complementary treatment strategy for existing sGC-directed therapies.Antioxid. Redox Signal. 26, 122–136.