Psoralen-fatty acid adducts activate melanocyte protein kinase C: a proposed mechanism for melanogenesis induced by 8-methoxypsoralen and ultraviolet A light

Authors

  • F. A. Anthony,

    Corresponding author
    1. Research & Development, Schering-Plough HealthCare Products, Inc., Memphis, TN, USA
    2. National Institute for Occupational Safety and Health (NIOSH), Division of Biomedical and Behavioral Science, Robert A. Taft Laboratories, Cincinnati, OH, USA
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  • H. M. Laboda,

    1. National Institute for Occupational Safety and Health (NIOSH), Division of Biomedical and Behavioral Science, Robert A. Taft Laboratories, Cincinnati, OH, USA
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  • M. E. Costlow

    1. National Institute for Occupational Safety and Health (NIOSH), Division of Biomedical and Behavioral Science, Robert A. Taft Laboratories, Cincinnati, OH, USA
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Research & Development, Schering-Plough HealthCare Products, Inc., 3030 Jackson Ave., Memphis, TN 38151, USA

Abstract

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.

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