Soluble guanylyl cyclase mediates noncanonical nitric oxide signaling by nitrosothiol transfer under oxidative stress.
Soluble guanylyl cyclase mediates noncanonical nitric oxide signaling by nitrosothiol transfer under oxidative stress.
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DOI：
10.1016/j.redox.2022.102425
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发表时间：
2022-09
期刊：
影响因子：
11.4
通讯作者：
Beuve, Annie
中科院分区：
文献类型：
--
作者：
Cui, Chuanlong;Wu, Changgong;Shu, Ping;Liu, Tong;Li, Hong;Beuve, Annie
可溶性鸟苷酸环化酶（GC 1）是一种α/β异源二聚体，在一氧化氮（NO）刺激下产生cGMP。NO-GC 1-cGMP通路对于心血管稳态是必不可少的，但被氧化应激破坏，这导致GC 1通过血红素氧化和特定半胱氨酸的S-亚硝化（SNO）对NO脱敏。我们发现在这些条件下，GC 1-α亚基通过将亚硝基硫醇转移到心脏和平滑肌细胞中的其他蛋白质（转亚硝化）来增加细胞S-亚硝化。GC 1 SNO靶点之一是硫氧还蛋白1（oTrx 1）的氧化形式，其通过GC 1与αC610作为SNO供体进行单向亚硝化。由于oTrx 1本身驱动转亚硝化，我们寻找并鉴定了GC 1和Trx 1靶向的SNO蛋白。我们发现，通过SNO-GC 1的小GTdR RhoA的转亚硝化需要oTrx 1作为亚硝基硫醇中继，这表明SNO-GC 1 → oTrx 1 →RhoA级联。RhoA信号通路被经典的NO-cGMP通路拮抗，在氧化条件下被GC 1-α依赖的S-亚硝化交替抑制。我们建议，SNO-GC 1，通过transnitrosation，介导的经典NO-cGMP途径的氧化引发的适应性反应。可溶性鸟苷酸环化酶（GC 1）是一种α/β异源二聚体酶，在NO刺激下产生cGMP。GC 1具有“兼职”功能，它催化S-亚硝基硫醇转移到200多种蛋白质的Cys，包括Trx 1。在不存在功能性GC 1异二聚体的情况下，可以通过GC 1-α亚基的特异性Cys单独进行转亚硝化。GC 1转亚硝化活性在氧化条件下发生，已知氧化条件会损害经典的NO-GC 1-cGMP途径。GC 1转亚硝化级联反应，有时被氧化的Trx 1放大，可以拯救氧化/脱敏的NO-cGMP途径。
Soluble guanylyl cyclase (GC1) is an α/β heterodimer producing cGMP when stimulated by nitric oxide (NO). The NO-GC1-cGMP pathway is essential for cardiovascular homeostasis but is disrupted by oxidative stress, which causes GC1 desensitization to NO by heme oxidation and S-nitrosation (SNO) of specific cysteines. We discovered that under these conditions, GC1-α subunit increases cellular S-nitrosation via transfer of nitrosothiols to other proteins (transnitrosation) in cardiac and smooth muscle cells. One of the GC1 SNO-targets was the oxidized form of Thioredoxin1 (oTrx1), which is unidirectionally transnitrosated by GC1 with αC610 as a SNO-donor. Because oTrx1 itself drives transnitrosation, we sought and identified SNO-proteins targeted by both GC1 and Trx1. We found that transnitrosation of the small GTPase RhoA by SNO-GC1 requires oTrx1 as a nitrosothiol relay, suggesting a SNO-GC1→oTrx1→RhoA cascade. The RhoA signaling pathway, which is antagonized by the canonical NO-cGMP pathway, was alternatively inhibited by GC1-α-dependent S-nitrosation under oxidative conditions. We propose that SNO-GC1, via transnitrosation, mediates adaptive responses triggered by oxidation of the canonical NO-cGMP pathway. Soluble guanylyl cyclase (GC1) is an α/β heterodimeric enzyme that produces cGMP in response to NO stimulation. GC1 has a “moonlighting” function, it catalyzes the transfer of S-nitrosothiols to Cys of over 200 proteins, including Trx1. Transnitrosation can be executed by specific Cys of the GC1-α subunit alone, in the absence of a functional GC1 heterodimer. GC1 transnitrosation activity takes place under oxidative conditions, known to compromise the canonical NO-GC1-cGMP pathway. GC1 transnitrosation cascades, sometimes amplified by oxidized Trx1, could rescue the oxidized/desensitized NO-cGMP pathway.
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影响因子：
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作者：
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影响因子：
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作者：
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影响因子：
64.5
作者：
Jia J;Arif A;Terenzi F;Willard B;Plow EF;Hazen SL;Fox PL
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影响因子：
5.8
作者：
Chen F;Wang Y;Rafikov R;Haigh S;Zhi WB;Kumar S;Doulias PT;Rafikova O;Pillich H;Chakraborty T;Lucas R;Verin AD;Catravas JD;She JX;Black SM;Fulton DJR
通讯作者：
Fulton DJR
DOI：
10.1073/pnas.0704898104
发表时间：
2007-07-10
影响因子：
11.1
作者：
Mitchell, Douglas A.;Morton, Sarah U.;Marletta, Michael A.
通讯作者：
Marletta, Michael A.