S-nitrosylation of endothelial nitric oxide synthase impacts erectile function
S-nitrosylation of endothelial nitric oxide synthase impacts erectile function
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内皮一氧化氮合酶的 S-亚硝基化影响勃起功能
DOI：
10.1038/s41443-018-0056-0
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发表时间：
2018
影响因子：
2.6
通讯作者：
L. Palmer
中科院分区：
文献类型：
--
作者：
P. Kavoussi;Ryan P. Smith;Janine L Oliver;R. Costabile;W. Steers;K. Brown;Kimberly Ronde;J. Lysiak;L. Palmer
神经元型和内皮型一氧化氮合酶（分别为nNOS和eNOS）在产生勃起功能所必需的一氧化氮生物活性方面起主要作用。已表明S - 亚硝基化可调节NOS活性。研究了阴茎中S - 亚硝基化NOS的存在以及NOS的S - 亚硝基化/去亚硝基化对勃起功能的影响。通过生物素转换试验及随后的蛋白质印迹分析鉴定NOS的S - 亚硝基化形式。通过海绵体神经持续电刺激（CCNES）评估S - 亚硝基谷胱甘肽还原酶缺陷型（GSNO +/−）和缺失型（GSNO −/−）小鼠的勃起功能。使用谷胱甘肽乙酯（GSHee）来调控S - 亚硝基化NOS的水平。采用免疫组织学和免疫荧光分析来确定eNOS和GSNO - R在海绵体组织中的位置。在小鼠未受刺激的阴茎中，eNOS和nNOS发生了S - 亚硝基化。CCNES导致eNOS的S - 亚硝基化呈时间依赖性增加，在阴茎疲软期观察到eNOS的S - 亚硝基化达到峰值。S - 亚硝基化的nNOS水平未改变。海绵体内注射GSHee可降低S - 亚硝基化的eNOS水平，延长达到最大海绵体内压（ICP）的时间。在小鼠和人类中，eNOS和GSNO - R共定位于海绵体的内皮。在CCNES过程中获得的ICP测量结果表明，GSNO - R +/−和GSNO - R −/−动物无法维持升高的ICP。结果表明，eNOS的S - 亚硝基化/去亚硝基化是在勃起功能过程中调节eNOS活性的重要机制。GSNO - R是参与eNOS去亚硝基化的关键酶。在阴茎勃起时观察到的eNOS的S - 亚硝基化（失活）增加可能启动一个导致阴茎疲软的循环。临床上，这可能表明S - 亚硝基化/去亚硝基化平衡的改变直接或间接导致勃起功能障碍。
Neuronal and endothelial nitric oxide synthases (nNOS and eNOS respectively) play major roles in generating the nitric oxide bioactivity necessary for erectile function. S-nitrosylation has been shown to regulate NOS activity. The presence of S-nitrosylated NOS in the penis and the impact of NOS S-nitrosylation/denitrosylation on erectile function were examined. S-nitrosylated forms of NOS were identified by biotin-switch assay followed by western blot analysis. Erectile function in S-nitrosoglutathione reductase deficient (GSNO+/−) and null (GSNO−/−) mice were assessed by continuous cavernous nerve electrical stimulation (CCNES). Glutathione ethyl ester (GSHee) was used to manipulate S-nitrosylated NOS levels. Immunohistological and immunofluorescence analyses were used to identify the location of eNOS and GSNO-R in corporal tissue. eNOS and nNOS were S-nitrosylated in unstimulated penises of the mice. CCNES resulted in a time-dependent increase in eNOS S-nitrosylation with peak eNOS S-nitrosylation observed during detumescence. S-nitrosylated nNOS levels were unchanged. Intracorporal injection of GSHee reduced S-nitrosylated eNOS levels, enhancing time to maximum intracorporal pressure (ICP). eNOS and GSNO-R co-localize to the endothelium of the corpus cavernosum in the mouse and the human. ICP measurements obtained during CCNES demonstrate GSNO-R+/− and GSNO-R−/− animals cannot maintain an elevated ICP. Results suggest eNOS S-nitrosylation/denitrosylation is an important mechanism regulating eNOS activity during erectile function. GSNO-R is a key enzyme involved in the eNOS denitrosylation. The increase in eNOS S-nitrosylation (inactivation) observed with tumescence may begin a cycle leading to detumescence. Clinically this may indicate that alterations in the balance of S-nitrosylation/denitrosylation either directly or indirectly contribute to erectile dysfunction.
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DOI：
10.1016/j.jsxm.2016.03.003
发表时间：
2016-05
期刊：
The journal of sexual medicine
影响因子：
--
作者：
Musicki B;Lagoda G;Goetz T;La Favor JD;Burnett AL
通讯作者：
Burnett AL
影响因子：
13.6
作者：
Foster MW;Hess DT;Stamler JS
通讯作者：
Stamler JS
一氧化氮对一氧化氮合酶的调节。
影响因子：
3.6
作者：
Rengasamy,A;Johns,RA
通讯作者：
Johns,RA
DOI：
10.1073/pnas.0407183102
发表时间：
2005-02-01
影响因子：
11.1
作者：
Champion, HC;Bivalacqua, TJ;Burnett, AL
通讯作者：
Burnett, AL
影响因子：
15.9
作者：
MURAD, F
通讯作者：
MURAD, F