Psoralen-fatty acid adducts activate melanocyte protein kinase C: a proposed mechanism for melanogenesis induced by 8-methoxypsoralen and ultraviolet A light.
Diacylglycerol, a protein kinase C activator, induces and enhances melanogenesis in vitro and in vivo, providing evidence that melanogenesis may be a protein kinase C-mediated process. Melanogenesis is also induced by ultraviolet A radiation and potentiated by a combination of 8-methoxypsoralen and ultraviolet A radiation. We incubated cultured normal human melanocytes with 8-methoxypsoralen, irradiated the cells with ultraviolet A radiation, and detected formation of 8-methoxypsoralen-phospholipid photoadducts. The 8-methoxypsoralen-phospholipid photoadducts isolated from melanocytes were substrates for phospholipase A2 to generate 8-methoxypsoralen-fatty acid adducts. We found that 8-methoxypsoralen-fatty acid photoadducts prepared in vitro could be substituted for diacylglycerol to activate protein kinase C in a cell-free system. We propose that 8-methoxypsoralen-fatty acid adducts activate protein kinase C to potentiate ultraviolet A radiation-induced melanogenesis. This proposal links melanogenesis mediated by protein kinase C with that induced by a combination of 8-methoxypsoralen and ultraviolet A radiation.
Anthony
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FA
Schering-Plough HealthCare Products, Inc., Memphis, TN 38151, USA.
Laboda
H M
HM
Costlow
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ME
D000818:Animals; D001095:Arachidonic Acids / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D002855:Chromatography, Thin Layer; D004075:Diglycerides / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D019787:Linoleic Acid / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D008543:Melanins / Q000096:biosynthesis* / Q000528:radiation effects; D008544:Melanocytes / Q000187:drug effects / Q000201:enzymology* / Q000528:radiation effects; D008730:Methoxsalen / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D010712:Phosphatidic Acids / Q000737:chemistry / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism; D017319:Photosensitizing Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011493:Protein Kinase C / Q000187:drug effects*; D019275:Radiopharmaceuticals; D014316:Tritium; D014466:Ultraviolet Rays; D017962:alpha-Linolenic Acid / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology
D001095:Arachidonic Acids; D004075:Diglycerides; D005227:Fatty Acids; D008543:Melanins; D010712:Phosphatidic Acids; D010743:Phospholipids; D017319:Photosensitizing Agents; D019275:Radiopharmaceuticals; D017962:alpha-Linolenic Acid; D014316:Tritium; D019787:Linoleic Acid; D011493:Protein Kinase C; D010741:Phospholipases A; D054467:Phospholipases A2; D008730:Methoxsalen