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Molecular Profile of Priapism Associated with Low Nitric Oxide Bioavailability
Journal of Proteome Research ( IF 3.8 ) Pub Date : 2018-02-12 00:00:00 , DOI: 10.1021/acs.jproteome.7b00657
Justin D. La Favor , Zongming Fu , Vidya Venkatraman 1 , Trinity J. Bivalacqua , Jennifer E. Van Eyk 1 , Arthur L. Burnett
Affiliation  

Priapism is a disorder in which prolonged penile erection persists uncontrollably, potentially leading to tissue damage. Priapism commonly afflicts patient populations with severely low nitric oxide (NO) bioavailability. Because NO is a primary mediator of erection, the molecular mechanisms involved in priapism pathophysiology associated with low NO bioavailability are not well-understood. The objective of this study was to identify dysregulated molecular targets and signaling pathways in penile tissue of a mouse model of low NO bioavailability that have potential relevance to priapism. Neuronal plus endothelial NO synthase double knockout mice (NOS1/3–/–) were used as a model of low NO bioavailability. Priapic-like activity was demonstrated in the NOS1/3–/– mice relative to wild-type (WT) mice by the measurement of prolonged erections following cessation of electrical stimulation of the cavernous nerve. Penile tissue was processed and analyzed by reverse-phase liquid chromatography tandem mass spectrometry. As a result, 1279 total proteins were identified and quantified by spectral counting, 46 of which were down-regulated and 110 of which were up-regulated in NOS1/3–/– versus WT (P < 0.05). Ingenuity Pathway Analysis of differentially expressed proteins revealed increased protein kinase A and G-protein coupled receptor signaling in NOS1/3–/– penises, which represent potential mechanisms contributing to priapism for secondary to low NO bioavailability.

中文翻译:

一氧化氮的生物利用度低相关的精神分裂症的分子概况

阴茎异常勃起是一种长期无法控制的阴茎勃起持续不断的疾病,可能导致组织损伤。狂妄症通常使一氧化氮(NO)生物利用度严重低下的患者群体饱受折磨。因为NO是勃起的主要介体,所以与NO的生物利用度低相关的阴茎异常病理生理学涉及的分子机制尚未得到很好的理解。这项研究的目的是确定低NO生物利用度的小鼠模型的阴茎组织中失调的分子靶标和信号传导途径,这些模型与阴茎异常勃勃症具有潜在的相关性。神经元和内皮一氧化氮合酶双敲除小鼠(NOS1 / 3 – / –)被用作低NO生物利用度的模型。在NOS1 / 3 – / –中显示了Priapic样的活动在停止电刺激海绵状神经后,通过测量勃起时间延长来测量小鼠相对于野生型(WT)小鼠的情况。通过反相液相色谱串联质谱法对阴茎组织进行处理和分析。结果,通过光谱计数鉴定和定量了1279种总蛋白,其中46种在NOS1 / 3 – / –相对于WT中被下调,而110种在WT中被上调(P <0.05)。差异表达蛋白质的独创性途径分析显示,NOS1 / 3 – / –阴茎中蛋白激酶A和G蛋白偶联受体信号增强,这代表了继发于NO低生物利用度的潜在原因。
更新日期:2018-02-13
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