Mechanism and biological relevance of blue-light (420-453 nm)-induced nonenzymatic nitric oxide generation from photolabile nitric oxide derivates in human skin in vitro and in vivo
Mechanism and biological relevance of blue-light (420-453 nm)-induced nonenzymatic nitric oxide generation from photolabile nitric oxide derivates in human skin in vitro and in vivo
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DOI：
10.1016/j.freeradbiomed.2013.09.022
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发表时间：
2013-12-01
影响因子：
7.4
通讯作者：
Suschek, Christoph V.
中科院分区：
文献类型：
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作者：
Oplaender, Christian;Deck, Annika;Suschek, Christoph V.
人体皮肤含有亚硝酸盐和S亚硫醇等不发光的一氧化氮(NO)衍生物，在UVA辐射下，它们会在高产量的NO形成下分解，并产生非特异性的生物反应，如局部血流量增加或血压降低。为了避免UVA辐射的损伤效应，我们在体内外研究了蓝光(420453 Nm)诱导人体皮肤中不耐光的一氧化氮衍生物产生非酶NO的机制和生物学意义。化学发光检测表明，在生理pH条件下，420或453 nm的蓝光可显著诱导S亚硝酸白蛋白和亚硝酸根水溶液生成NO，其机制尚未完全确定。电子顺磁共振波谱分析显示，蓝光照射可显著增加皮肤组织中游离NO的水平。根据CLD在健康志愿者体内的检测，蓝光照射人皮肤后，受照射皮肤区域的NO显著释放，并从皮肤表面显著移位到下面的组织中。同时，蓝光照射导致局部皮肤血流量迅速而显著增加，这是用显微光导分光光度法无创检测到的。中等剂量的蓝光照射人皮肤后，皮肤NO的生成显著增加，NO依赖的局部生物反应也明显增加，即血流增加。这种效应归因于蓝光诱导皮肤耐光性NO衍生物释放NO。因此，与UVA相比，蓝光诱导的NO产生可能被用于治疗基于生理NO产生或生物利用度受损的全身和局部血流动力学疾病。(C)2013 Elsevier Inc.保留所有权利。
Human skin contains photolabile nitric oxide (NO) derivates such as nitrite and S-nitrosothiols, which upon UVA radiation decompose under high-output NO formation and exert NO-specific biological responses such as increased local blood flow or reduced blood pressure. To avoid the injurious effects of UVA radiation, we here investigated the mechanism and biological relevance of blue-light (420453 nm)-induced nonenzymatic NO generation from photolabile nitric oxide derivates in human skin in vitro and in vivo. As quantified by chemiluminescence detection (CLD), at physiological pH blue light at 420 or 453 nm induced a significant NO formation from S-nitrosoalbumin and also from aqueous nitrite solutions by a to-date not entirely identified Cu1+ -dependent mechanism. As detected by electron paramagnetic resonance spectrometry in vitro with human skin specimens, blue light irradiation significantly increased the intradermal levels of free NO. As detected by CLD in vivo in healthy volunteers, irradiation of human skin with blue light induced a significant emanation of NO from the irradiated skin area as well as a significant translocation of NO from the skin surface into the underlying tissue. In parallel, blue light irradiation caused a rapid and significant rise in local cutaneous blood flow as detected noninvasively by using micro-light-guide spectrophotometry. Irradiation of human skin with moderate doses of blue light caused a significant increase in enzyme-independent cutaneous NO formation as well as NO-dependent local biological responses, i.e., increased blood flow. The effects were attributed to blue-light-induced release of NO from cutaneous photolabile NO derivates. Thus, in contrast to UVA, blue-light-induced NO generation might be therapeutically used in the treatment of systemic and local hemodynamic disorders that are based on impaired physiological NO production or bioavailability. (C) 2013 Elsevier Inc. All rights reserved.