title: Ultraviolet radiation-induced melanogenesis in human melanocytes. Effects of modulating protein kinase C.
abstract: The mechanism by which ultraviolet radiation induces melanogenesis in epidermal melanocytes is unknown. Previous observations that in cultured human melanocytes 1-oleoyl-2-acetylglycerol augmented both basal and ultraviolet radiation-induced melanogenesis, suggested that the responses were mediated via protein kinase C. However, paradoxically the phorbol ester TPA was without effect. Therefore, the present study has examined the involvement of protein kinase C in melanogenesis. Analysis of the isozyme profile of human melanocytes revealed the presence of protein kinase C alpha, beta I, epsilon and zeta but not the isozyme eta. Following exposure to 500 nM TPA for 24 hours, isozymes alpha, beta I and epsilon were downregulated, but zeta was unaffected. Similar isozyme profiles were observed in S91 and SKMEL3 melanoma cells. The melanogenic responses to 1-oleoyl-2-acetylglycerol and ultraviolet radiation were unaffected by inhibition of protein kinase C with Ro31-8220, or ablation by downregulation with 500 nM TPA, in human melanocytes and melanoma cells. 1-Oleoyl-2-acetylglycerol had no effect on protein kinase C activity in human melanocytes, as measured by rapid phosphorylation of the 80 kDa protein myristoylated alanine-rich C kinase substrate (MARCKS). Ultraviolet radiation induced a small increase in MARCKS protein phosphorylation but this effect was inhibited by pretreatment for 24 hours with 500 nM TPA, which had no effect on ultraviolet-induced melanogenesis. Overall, these findings indicate that 1-oleoyl-2-acetylglycerol and ultraviolet radiation activate melanogenesis via protein kinase C-independent pathways.
authors.affiliation: University Department of Dermatology, Liverpool, UK.
authors.forename: C J
authors.initials: CJ
authors.lastname: Carsberg
authors.forename: H M
authors.initials: HM
authors.lastname: Warenius
authors.forename: P S
authors.initials: PS
authors.lastname: Friedmann
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D016475:3T3 Cells / Q000528:radiation effects; D000818:Animals; D004075:Diglycerides / Q000494:pharmacology; D004790:Enzyme Induction / Q000528:radiation effects; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000502:physiology*; D008543:Melanins / Q000096:biosynthesis*; D008544:Melanocytes / Q000378:metabolism / Q000528:radiation effects*; D008545:Melanoma / Q000473:pathology; D008546:Melanoma, Experimental / Q000473:pathology; D008565:Membrane Proteins; D051379:Mice; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D010766:Phosphorylation / Q000528:radiation effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D011499:Protein Processing, Post-Translational / Q000528:radiation effects; D011506:Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000528:radiation effects; D012878:Skin Neoplasms / Q000473:pathology; D013657:Taurodeoxycholic Acid / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014466:Ultraviolet Rays
chemical_list: D004075:Diglycerides; D007211:Indoles; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes; C000619710:MARCKS protein, human; C000619711:Marcks protein, mouse; D008543:Melanins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D011506:Proteins; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D013657:Taurodeoxycholic Acid; C038237:1-oleoyl-2-acetylglycerol; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D015056:1-Methyl-3-isobutylxanthine; C064758:Ro 31-8220