Evidence for a role of nitric oxide in the mediation of antiproliferative UVA effects in keratinocytes

• Published in: Pharmacological research 2002-03, Vol.45 (3), p.229-233
• Main Authors: Podhaisky, Hans-Peter, Klapperstück, Thomas, Riemschneider, Stephan, Wohlrab, Wolfgang
• Format: Article
• Language: English
• Subjects: Antioxidants - pharmacology; Biopterins - analogs & derivatives; Biopterins - pharmacology; Cell Division - radiation effects; Cell Survival - radiation effects; Cells, Cultured; Cyclic N-Oxides - pharmacology; DNA - biosynthesis; Dose-Response Relationship, Radiation; Free Radical Scavengers - pharmacology; Humans; Imidazoles - pharmacology; Keratinocytes - drug effects; Keratinocytes - metabolism; Keratinocytes - radiation effects; Nitric Oxide - biosynthesis; Nitric Oxide Synthase - antagonists & inhibitors; Nitric Oxide Synthase - metabolism; nitric oxide, human keratinocytes, proliferation, ultraviolet A radiation, cytoprotection; omega-N-Methylarginine - pharmacology; Ultraviolet Rays - adverse effects
• ISSN: 1043-6618; 1096-1186
• DOI: 10.1006/phrs.2001.0939

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 μM) or the NO synthase inhibitor N(G)-monomethyl-l-arginine (l-NMMA, 30–300 μM) 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 μM) 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.