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The impact of N-nitrosomelatonin as nitric oxide donor in cell culture experiments.
Journal of Pineal Research ( IF 8.3 ) Pub Date : 2008-08-05 , DOI: 10.1111/j.1600-079x.2008.00622.x
Utta Berchner-Pfannschmidt 1 , Suzan Tug , Buena Trinidad , Maria Becker , Felix Oehme , Ingo Flamme , Joachim Fandrey , Michael Kirsch
Affiliation  

N-nitrosomelatonin (NOMela) is well-known for its capabilities of transnitrosating nucleophiles such as thiols and ascorbate, thereby generating nitric oxide (NO)-releasing compounds. It is unknown, however, whether NOMela can be successfully applied as a precursor of NO in a complex biological environment like a cell culture system. NO donors may be useful to induce the transcription factor hypoxia inducible factor 1 (HIF-1), which coordinates the protection of cells and tissues from the lack of oxygen (hypoxia). In this study, the effects of NOMela in an in vitro cell-free assay [NO-release, inhibition of prolylhydroxylase1 (PHD1)] and in living cells (upregulation of HIF-1, reduction of HIF-1 hydroxylation, upregulation of the HIF-1-target gene PHD2) were compared with those of the frequently applied NO donor S-nitrosoglutathione (GSNO) under normoxic and hypoxic conditions. In contrast to GSNO, NOMela released NO in a predictable manner and this release in vitro was found to be independent of the composition of the buffer system. The NOMela-mediated effects in oxygenated cells were in all cases comparable to the hypoxic response, whereas unphysiological strong effects were observed with GSNO. Probably, because of the antioxidative power of the NOMela-dependent formation of melatonin, cells were completely protected against the attack of reactive nitrogen oxygen species, which are generated by autoxidation of NO. In conclusion, NOMela had to be an excellent NO precursor for cells in culture and potentially tissues.

中文翻译:

N-硝化褪黑激素作为一氧化氮供体在细胞培养实验中的影响。

N-硝化褪黑激素(NOMela)具有将亲核试剂(例如硫醇和抗坏血酸盐)进行亚硝化,从而生成可释放一氧化氮(NO)的化合物的能力,因此众所周知。但是,未知的是,NOMela是否可以成功地用作复杂的生物环境(如细胞培养系统)中的NO的前体。NO供体可能可用于诱导转录因子缺氧诱导因子1(HIF-1),该因子可协调保护细胞和组织免受缺氧的影响(缺氧)。在这项研究中,NOMela在体外无细胞试验中的作用[NO释放,抑制脯氨酰羟化酶1(PHD1)]和在活细胞中的作用(HIF-1上调,HIF-1羟基化减少,在常氧和低氧条件下,将HIF-1靶基因PHD2的高表达与经常使用的NO供体S-亚硝基谷胱甘肽(GSNO)的表达进行了比较。与GSNO相比,NOMela以可预测的方式释放NO,并且发现这种释放在体外与缓冲系统的组成无关。在所有情况下,NOMela介导的氧化细胞作用均与低氧反应相当,而GSNO则观察到非生理性强作用。可能是由于NOMela依赖的褪黑激素形成具有抗氧化能力,因此可以完全保护细胞免受NO的自动氧化产生的活性氮氧的侵蚀。总之,NOMela必须是培养细胞和潜在组织中极好的NO前体。与GSNO相比,NOMela以可预测的方式释放NO,并且发现这种释放在体外与缓冲系统的组成无关。在所有情况下,NOMela介导的氧化细胞作用均与低氧反应相当,而GSNO则观察到非生理性强作用。可能是由于NOMela依赖的褪黑激素形成具有抗氧化能力,因此可以完全保护细胞免受NO的自动氧化产生的活性氮氧的侵蚀。总之,NOMela必须是培养细胞和潜在组织中极好的NO前体。与GSNO相比,NOMela以可预测的方式释放NO,并且发现这种释放在体外与缓冲系统的组成无关。在所有情况下,NOMela介导的氧化细胞作用均与低氧反应相当,而GSNO则观察到非生理性强作用。可能是由于NOMela依赖的褪黑激素形成具有抗氧化能力,因此可以完全保护细胞免受NO的自动氧化产生的活性氮氧的侵蚀。总之,NOMela必须是培养细胞和潜在组织中极好的NO前体。在所有情况下,NOMela介导的氧化细胞作用均与低氧反应相当,而GSNO则观察到非生理性强作用。可能是由于NOMela依赖的褪黑激素形成具有抗氧化能力,因此可以完全保护细胞免受NO的自动氧化产生的活性氮氧的侵蚀。总之,NOMela必须是培养细胞和潜在组织中极好的NO前体。在所有情况下,NOMela介导的氧化细胞作用均与低氧反应相当,而GSNO则观察到非生理性强作用。可能是由于NOMela依赖的褪黑激素形成具有抗氧化能力,因此可以完全保护细胞免受NO的自动氧化产生的活性氮氧的侵蚀。总之,NOMela必须是培养细胞和潜在组织中极好的NO前体。
更新日期:2019-11-01
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