Enzyme-independent nitric oxide formation during UVA challenge of human skin: characterization, molecular sources, and mechanisms.
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.
Paunel
Adnana N
AN
Institute of Molecular Medicine, Department of Immunobiology, Heinrich-Heine-University of Düsseldorf, P.O. Box 101007, D-40001 Düsseldorf, Germany.
Dejam
André
A
Thelen
Sven
S
Kirsch
Michael
M
Horstjann
Markus
M
Gharini
Putrika
P
Mürtz
Manfred
M
Kelm
Malte
M
de Groot
Herbert
H
Kolb-Bachofen
Victoria
V
Suschek
Christoph V
CV
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
D009566:Nitrates; D009573:Nitrites; D009603:Nitroso Compounds; D013438:Sulfhydryl Compounds; D009569:Nitric Oxide; D006152:Cyclic GMP