title: 2,4,6-Octatrienoic acid is a novel promoter of melanogenesis and antioxidant defence in normal human melanocytes via PPAR-γ activation.
abstract: 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.
authors.affiliation: Laboratory of Cutaneous Physiopathology and Integrated Center of Metabolomics Research, San Gallicano Dermatologic Institute (IRCCS) Rome, Italy.
authors.forename: Enrica
authors.initials: E
authors.lastname: Flori
authors.forename: Arianna
authors.initials: A
authors.lastname: Mastrofrancesco
authors.forename: Daniela
authors.initials: D
authors.lastname: Kovacs
authors.forename: Yuval
authors.initials: Y
authors.lastname: Ramot
authors.forename: Stefania
authors.initials: S
authors.lastname: Briganti
authors.forename: Barbara
authors.initials: B
authors.lastname: Bellei
authors.forename: Ralf
authors.initials: R
authors.lastname: Paus
authors.forename: Mauro
authors.initials: M
authors.lastname: Picardo
mesh_terms: D000975:Antioxidants / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D004817:Epidermis / Q000187:drug effects / Q000502:physiology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D020868:Gene Silencing / Q000187:drug effects; D006801:Humans; D008297:Male; D008543:Melanins / Q000096:biosynthesis*; D008544:Melanocytes / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology*; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics / Q000378:metabolism; D014442:Monophenol Monooxygenase / Q000096:biosynthesis / Q000235:genetics; D009924:Organ Culture Techniques; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012535:Scalp / Q000187:drug effects / Q000502:physiology; D012880:Skin Pigmentation / Q000187:drug effects
chemical_list: D000975:Antioxidants; D005231:Fatty Acids, Unsaturated; D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; D047495:PPAR gamma; D012333:RNA, Messenger; C062198:octa-2,4,6-trienoic acid; D002374:Catalase; D014442:Monophenol Monooxygenase