2,4,6-Octatrienoic acid is a novel promoter of melanogenesis and antioxidant defence in normal human melanocytes via PPAR-γ activation

Authors

  • Enrica Flori,

    1.  Laboratory of Cutaneous Physiopathology and Integrated Center of Metabolomics Research, San Gallicano Dermatologic Institute (IRCCS) Rome, Italy
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  • Arianna Mastrofrancesco,

    1.  Laboratory of Cutaneous Physiopathology and Integrated Center of Metabolomics Research, San Gallicano Dermatologic Institute (IRCCS) Rome, Italy
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  • Daniela Kovacs,

    1.  Laboratory of Cutaneous Physiopathology and Integrated Center of Metabolomics Research, San Gallicano Dermatologic Institute (IRCCS) Rome, Italy
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  • Yuval Ramot,

    1.  Department of Dermatology, Hadassah University, Jerusalem, Israel
    2.  Department of Dermatology, University of Lübeck, Lübeck, Germany
    3.  School of Translational Medicine, University of Manchester, Manchester, UK
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  • Stefania Briganti,

    1.  Laboratory of Cutaneous Physiopathology and Integrated Center of Metabolomics Research, San Gallicano Dermatologic Institute (IRCCS) Rome, Italy
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  • Barbara Bellei,

    1.  Laboratory of Cutaneous Physiopathology and Integrated Center of Metabolomics Research, San Gallicano Dermatologic Institute (IRCCS) Rome, Italy
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  • Ralf Paus,

    1.  Department of Dermatology, University of Lübeck, Lübeck, Germany
    2.  School of Translational Medicine, University of Manchester, Manchester, UK
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  • Mauro Picardo

    1.  Laboratory of Cutaneous Physiopathology and Integrated Center of Metabolomics Research, San Gallicano Dermatologic Institute (IRCCS) Rome, Italy
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  • Enrica Flori and Arianna Mastrofrancesco contributed equally to this work.

Mauro Picardo, e-mail: picardo@ifo.it

Summary

Given the importance of the tanning response in protecting human skin from the harmful effects of UV radiation, one important research priority is to identify novel molecules that are capable of promoting pigmentation and/or antioxidant defence. Parrodienes share some structural features with carotenoids and retinoids, stimulate cell antioxidant defence and counteract senescence-like phenotype in fibroblasts. We selected the parrodiene-derivative 2,4,6-octatrienoic acid (Octa) to study its impact on key parameters of melanogenesis and antioxidant defence in organ-cultured human skin and in normal human melanocytes. Octa promoted melanogenesis by up-regulating tyrosinase and microphthalmia-associated transcription factor expression. This correlated with an increase of melanin content in both human epidermis in situ and cultured human epidermal melanocytes. Moreover, Octa increased the biological antioxidant potential content and the expression and activity of catalase. Activation of peroxisome proliferator-activated receptor (PPAR)-γ was necessary to evoke these effects. These data strongly encourage the systematic study of Octa as a novel candidate promoter of human skin photoprotection.

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