A natural compound harmine decreases melanin synthesis through regulation of the DYRK1A/NFATC3 pathway.

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  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: Netherlands NLM ID: 9011485 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-569X (Electronic) Linking ISSN: 09231811 NLM ISO Abbreviation: J Dermatol Sci Subsets: MEDLINE
    • Publication Information:
      Original Publication: Amsterdam : Elsevier, c1990-
    • Subject Terms:
      Harmine/*pharmacology ; Melanins/*antagonists & inhibitors ; NFATC Transcription Factors/*metabolism ; Protein Serine-Threonine Kinases/*antagonists & inhibitors ; Protein-Tyrosine Kinases/*antagonists & inhibitors ; Skin Lightening Preparations/*pharmacology; Cell Line, Tumor ; Gene Knockdown Techniques ; Humans ; Melanins/biosynthesis ; Melanocytes/drug effects ; Melanocytes/metabolism ; NFATC Transcription Factors/genetics ; Primary Cell Culture ; Protein Serine-Threonine Kinases/metabolism ; Protein-Tyrosine Kinases/metabolism ; Signal Transduction/drug effects ; Skin/cytology ; Skin/metabolism ; Skin Pigmentation/drug effects ; Dyrk Kinases
    • Abstract:
      Background: Melanin plays important roles in determining human skin color and protecting human skin cells against harmful ultraviolet light. However, abnormal hyperpigmentation in some areas of the skin may become aesthetically unpleasing, resulting in the need for effective agents or methods to regulate undesirable hyperpigmentation.
      Objective: We investigated the effect of harmine, a natural harmala alkaloid belonging to the beta-carboline family, on melanin synthesis and further explored the signaling pathways involved in its mechanism of action.
      Methods: Human MNT-1 melanoma cells and human primary melanocytes were treated with harmine, chemical inhibitors, small interfering RNAs, or mammalian expression vectors. Cell viability, melanin content, and expression of various target molecules were assessed.
      Results: Harmine decreased melanin synthesis and tyrosinase expression in human MNT-1 melanoma cells. Inhibition of DYRK1A, a harmine target, decreased melanin synthesis and tyrosinase expression. Further studies revealed that nuclear translocation of NFATC3, a potential DYRK1A substrate, was induced via the harmine/DYRK1A pathway and that NFATC3 knockdown increased melanin synthesis and tyrosinase expression. Suppression of melanin synthesis and tyrosinase expression via the harmine/DYRK1A pathway was significantly attenuated by NFATC3 knockdown. Furthermore, harmine also decreased melanin synthesis and tyrosinase expression through regulation of NFATC3 in human primary melanocytes.
      Conclusion: Our results indicate that harmine decreases melanin synthesis through regulation of the DYRK1A/NFATC3 pathway and suggest that the DYRK1A/NFATC3 pathway may be a potential target for the development of depigmenting agents.
      (Copyright © 2021 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.)
    • Contributed Indexing:
      Keywords: DYRK1A; Harmine; Melanin; NFATC3; Tyrosinase
    • Accession Number:
      0 (Melanins)
      0 (NFATC Transcription Factors)
      0 (NFATC3 protein, human)
      0 (Skin Lightening Preparations)
      4FHH5G48T7 (Harmine)
      EC 2.7.10.1 (Protein-Tyrosine Kinases)
      EC 2.7.11.1 (Protein Serine-Threonine Kinases)
    • Publication Date:
      Date Created: 20210525 Date Completed: 20210913 Latest Revision: 20231213
    • Publication Date:
      20231215
    • Accession Number:
      10.1016/j.jdermsci.2021.05.003
    • Accession Number:
      34030962