Evidence for a role of nitric oxide in the mediation of antiproliferative UVA effects in keratinocytes.
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.
Podhaisky
Hans-Peter
HP
Department of Dermatology, Martin-Luther-University Halle-Wittenberg, Ernst-Kromayer Strasse 5-6, D-06097 Halle, Germany. hans-peter.podhaisky@gmx.de
Klapperstück
Thomas
T
Riemschneider
Stephan
S
Wohlrab
Wolfgang
W
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
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