Photochemistry of nitric oxide andS-nitrosothiols in human skin

Photochemistry of nitric oxide andS-nitrosothiols in human skin
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DOI:
10.1007/s00418-020-01858-w
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发表时间:
2020-06-01
影响因子:
2.3
通讯作者:
Weller, Richard B.
Weller, Richard B.
中科院分区:
生物学3区
文献类型:
--
作者:
Pelegrino, Milena T.;Paganotti, Andre;Weller, Richard B.

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一氧化氮(NO)与血管舒张、巨噬细胞细胞毒性和伤口愈合等广泛的生理过程有关。人体皮肤含有NO前体(NOx)。它们主要由亚硝酸盐(NO2-),硝酸盐(NO3-)和-亚硝基硫醇(RSNOs)组成,形成了大量的NO储存。人体皮肤中的这些NO(x)储存可以在紫外线(UV)照射下将NO动员到血液中。本研究的主要目的是评估产生NO的最有效紫外波长,并将其与水溶液中各种NO前体进行比较。此外,紫外线可能会改变人体皮肤上的RSNO含量。首先,我们将NO(2)(-)和NO(3)(-)的纯水溶液以及NO(2)(-)与谷胱甘肽、NO(3)(-)与亚硝基谷胱甘肽(GSNO)的混合物照射,以确定这些物种单独释放NO的特征。我们依次评估了人体皮肤切片上NO的生成情况。从多余的整形手术样本中获得人体皮肤,使用选择性NO电化学传感器进行NO和RSNO测量。数据显示,紫外线可触发皮肤生成NO,峰值在280 ~ 285 nm (UVB范围)。我们还观察到辐照后人体皮肤中有明显的RSNO形成,在320 nm(紫外区)和700 nm(可见光区)处有峰值。使用NO(2)(-)和硫醇(RSHs)清除剂对人体皮肤切片进行预处理,证实了这些分子在RSNO形成中的重要作用。这些发现对潜在的新疗法的临床试验具有重要意义。
Nitric oxide (NO) is related to a wide range of physiological processes such as vasodilation, macrophages cytotoxicity and wound healing. The human skin contains NO precursors (NOx). Those are mainly composed of nitrite (NO2-), nitrate (NO3-), andS-nitrosothiols (RSNOs) which forms a large NO store. These NO(x)stores in human skin can mobilize NO to blood stream upon ultraviolet (UV) light exposure. The main purpose of this study was to evaluate the most effective UV light wavelength to generate NO and compare it to each NO precursor in aqueous solution. In addition, the UV light might change the RSNO content on human skin. First, we irradiated pure aqueous solutions of NO(2)(-)and NO(3)(-)and mixtures of NO(2)(-)and glutathione and NO(3)(-)andS-nitrosoglutathione (GSNO) to identify the NO release profile from those species alone. In sequence, we evaluated the NO generation profile on human skin slices. Human skin was acquired from redundant plastic surgical samples and the NO and RSNO measurements were performed using a selective NO electrochemical sensor. The data showed that UV light could trigger the NO generation in skin with a peak at 280-285 nm (UVB range). We also observed a significant RSNO formation in irradiated human skin, with a peak at 320 nm (UV region) and at 700 nm (visible region). Pre-treatment of the human skin slice using NO(2)(-)and thiol (RSHs) scavengers confirmed the important role of these molecules in RSNO formation. These findings have important implications for clinical trials with potential for new therapies.