title: Evidence for a role of nitric oxide in the mediation of antiproliferative UVA effects in keratinocytes.
abstract: Using cultured human keratinocytes, the present study investigates the role of nitric oxide (NO) in the mediation of the antiproliferative effects of ultraviolet light A (UVA). UVA treatment of cells (3-21 J cm (-2)) caused a time- and dose-dependent increase in nitrite formation in a micromolar range. This effect was accompanied by a decrease in DNA synthesis by 53.5%. Moreover, UVA treatment slightly reduced cell viability by 23.8%. Preincubation of keratinocytes with the NO scavenger 4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide (PTIO, 10-100 microM) or the NO synthase inhibitor N(G)-monomethyl-l-arginine (l-NMMA, 30-300 microM) significantly diminished the UVA-induced increase in nitrite. PTIO as well as l-NMMA partially protected keratinocytes from UVA-induced antiproliferative effects and increased DNA synthesis by 67 or 49% of the control. The co-application of UVA irradiation (10 J cm (-2)) and the essential cofactor of NO synthases tetrahydrobiopetrin (BH4, 500 microM) led to an overadditive increase in the release of nitrite as well as to a decrease in DNA synthesis. These results imply that NO is involved in the antiproliferative UVA effects in keratinocytes.
authors.affiliation: Department of Dermatology, Martin-Luther-University Halle-Wittenberg, Ernst-Kromayer Strasse 5-6, D-06097 Halle, Germany. hans-peter.podhaisky@gmx.de
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Podhaisky
authors.forename: Thomas
authors.initials: T
authors.lastname: Klapperstück
authors.forename: Stephan
authors.initials: S
authors.lastname: Riemschneider
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wohlrab
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D001708:Biopterins / Q000031:analogs & derivatives* / Q000494:pharmacology; D002455:Cell Division / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects; D002478:Cells, Cultured; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D004307:Dose-Response Relationship, Radiation; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects*; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D014466:Ultraviolet Rays / Q000009:adverse effects*; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D007093:Imidazoles; C079391:2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide; D001708:Biopterins; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D004247:DNA; D019001:Nitric Oxide Synthase; C003402:sapropterin