title: Enzyme-independent nitric oxide formation during UVA challenge of human skin: characterization, molecular sources, and mechanisms.
abstract: Many of the local UV-induced responses including erythema and edema formation, inflammation, premature aging, and immune suppression can be influenced by nitric oxide synthase (NOS)-produced NO which is known to play a pivotal role in cutaneous physiology. Besides NOS-mediated NO production, UV radiation might trigger an enzyme-independent NO formation in human skin by a mechanism comprising the decomposition of photo-reactive nitrogen oxides. Therefore, we have examined the chemical-storage forms of potential NO-generating agents, the mechanisms and kinetics of their decomposition, and their biological relevance. In normal human skin specimens we find nitrite and S-nitrosothiols (RSNO) at concentrations 25- or 360-fold higher than those found in plasma of healthy volunteers. UVA irradiation of human skin leads to high-output formation of bioactive NO due to photo-decomposition of RSNO and nitrite which represents the primary basis for NO formation during UVA exposure. Interestingly, reduced thiols strongly augment photo-decomposition of nitrite and are essential for maximal NO release. The enzyme-independent NO formation found in human skin opens a completely new field in cutaneous physiology and will extend our understanding of mechanisms contributing to skin aging, inflammation, and cancerogenesis.
authors.affiliation: Institute of Molecular Medicine, Department of Immunobiology, Heinrich-Heine-University of Düsseldorf, P.O. Box 101007, D-40001 Düsseldorf, Germany.
authors.forename: Adnana N
authors.initials: AN
authors.lastname: Paunel
authors.forename: André
authors.initials: A
authors.lastname: Dejam
authors.forename: Sven
authors.initials: S
authors.lastname: Thelen
authors.forename: Michael
authors.initials: M
authors.lastname: Kirsch
authors.forename: Markus
authors.initials: M
authors.lastname: Horstjann
authors.forename: Putrika
authors.initials: P
authors.lastname: Gharini
authors.forename: Manfred
authors.initials: M
authors.lastname: Mürtz
authors.forename: Malte
authors.initials: M
authors.lastname: Kelm
authors.forename: Herbert
authors.initials: H
authors.lastname: de Groot
authors.forename: Victoria
authors.initials: V
authors.lastname: Kolb-Bachofen
authors.forename: Christoph V
authors.initials: CV
authors.lastname: Suschek
mesh_terms: D000818:Animals; D006152:Cyclic GMP / Q000096:biosynthesis; D006801:Humans; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D009573:Nitrites / Q000378:metabolism; D009603:Nitroso Compounds / Q000378:metabolism; D051381:Rats; D012867:Skin / Q000378:metabolism* / Q000528:radiation effects*; D013438:Sulfhydryl Compounds / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: D009566:Nitrates; D009573:Nitrites; D009603:Nitroso Compounds; D013438:Sulfhydryl Compounds; D009569:Nitric Oxide; D006152:Cyclic GMP