title: 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.
abstract: 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 (420-453 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 Cu(1+)-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.
authors.affiliation: Department of Trauma and Hand Surgery, Medical Faculty, University Hospital, Heinrich-Heine-University Düsseldorf, 40225 Düsseldorf, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Opländer
authors.affiliation: Department of Plastic and Reconstructive Surgery, Hand Surgery, and Burn Center, Medical Faculty, RWTH Aachen University, Aachen, Germany.
authors.forename: Annika
authors.initials: A
authors.lastname: Deck
authors.affiliation: Department of Trauma and Hand Surgery, Medical Faculty, University Hospital, Heinrich-Heine-University Düsseldorf, 40225 Düsseldorf, Germany.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Volkmar
authors.affiliation: Institute of Physiological Chemistry, University Hospital, Essen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Kirsch
authors.affiliation: Innovative Technologies, Philips Technologie GmbH, Aachen, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Liebmann
authors.affiliation: Innovative Technologies, Philips Technologie GmbH, Aachen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Born
authors.affiliation: Philips Research, Eindhoven, The Netherlands.
authors.forename: Frank
authors.initials: F
authors.lastname: van Abeelen
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Ernst E
authors.initials: EE
authors.lastname: van Faassen
authors.affiliation: Institute of Biochemistry and Molecular Biology I, Medical Faculty, University Hospital, Heinrich-Heine-University Düsseldorf, 40225 Düsseldorf, Germany.
authors.forename: Klaus-Dietrich
authors.initials: KD
authors.lastname: Kröncke
authors.affiliation: Department of Trauma and Hand Surgery, Medical Faculty, University Hospital, Heinrich-Heine-University Düsseldorf, 40225 Düsseldorf, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Windolf
authors.affiliation: Department of Trauma and Hand Surgery, Medical Faculty, University Hospital, Heinrich-Heine-University Düsseldorf, 40225 Düsseldorf, Germany. Electronic address: suschek@uni-duesseldorf.de.
authors.forename: Christoph V
authors.initials: CV
authors.lastname: Suschek
mesh_terms: D000328:Adult; D000818:Animals; D045744:Cell Line, Tumor; D003300:Copper / Q000737:chemistry; D006152:Cyclic GMP / Q000096:biosynthesis / Q000737:chemistry; D005260:Female; D006801:Humans; D008027:Light; D049449:Luminescence; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000097:blood / Q000737:chemistry; D009573:Nitrites / Q000737:chemistry*; D009603:Nitroso Compounds / Q000737:chemistry; D010789:Phototherapy / Q000379:methods; D051381:Rats; D026403:S-Nitrosothiols / Q000737:chemistry*; D012710:Serum Albumin, Bovine / Q000737:chemistry; D012867:Skin / Q000378:metabolism* / Q000528:radiation effects*
chemical_list: D009573:Nitrites; D009603:Nitroso Compounds; D026403:S-Nitrosothiols; C091665:S-nitrosoalbumin; D012710:Serum Albumin, Bovine; D009569:Nitric Oxide; D003300:Copper; D006152:Cyclic GMP
keywords: CLD; EPR; Fe–DETC; Free radicals; Human skin; MNIC; Nitric oxide; Nitrite; Nitroso compounds; Photodecomposition; RS-NO; S-nitrosothiols; cGMP; chemiluminescence detection; electron paramagnetic resonance; guanosine 3′,5′-cyclic monophosphate; iron–diethyldithiocarbamate; mononitrosyl–iron complex