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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• 作者：Christian Opl盲nder ; Annika Deck ; Christine M. Volkmar ; Michael Kirsch ; J枚rg Liebmann ; Matthias Born ; Frank van Abeelen ; Ernst E. van Faassen ; Klaus-Dietrich Kr枚ncke ; Joachim Windolf ; Christoph V. Suschek
• 关键词：CLD ; chemiluminescence detection ; EPR ; electron paramagnetic resonance ; RS-NO ; S-nitrosothiols ; cGMP ; guanosine 3&prime ; 5&prime ; -cyclic monophosphate ; Fe&ndash ; DETC ; iron&ndash ; diethyldithiocarbamate ; MNIC ; mononitrosyl&ndash ; iron complex
• 刊名：Free Radical Biology and Medicine
• 出版年：December, 2013
• 年：2013
• 卷：65
• 期：Complete
• 页码：1363-1377
• 全文大小：3259 K

文摘

Human skin contains photolabile nitric oxide (NO) derivates such as nitrite and m>Sm>-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 (420-453 nm)-induced nonenzymatic NO generation from photolabile nitric oxide derivates in human skin m>in vitrom> and m>in vivom>. As quantified by chemiluminescence detection (CLD), at physiological pH blue light at 420 or 453 nm induced a significant NO formation from m>Sm>-nitrosoalbumin and also from aqueous nitrite solutions by a to-date not entirely identified Cu¹⁺-dependent mechanism. As detected by electron paramagnetic resonance spectrometry m>in vitrom> with human skin specimens, blue light irradiation significantly increased the intradermal levels of free NO. As detected by CLD m>in vivom> 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.