Spermidine promotes melanin production through an MITF signalling pathway

Cell Biochem Funct. 2021 Jun;39(4):536-545. doi: 10.1002/cbf.3619. Epub 2021 Jan 25.

Abstract

Melanin plays an important role in determining skin colour. Apoptosis of melanocytes and defect in melanin production cause vitiligo. Various studies have been conducted to treat the disease, but its treatment is still difficult. Therefore, this study aimed to investigate the effect of spermidine, which is known as an inhibitor of ageing-related oxidized proteins, on melanogenesis. Even though spermidine above 50 μM had no effect on antioxidant activity and DOPA oxidation, it displayed tyrosinase activity. However, spermidine at 2000 μM was cytotoxic in B16F1 cells using MTT assay. Spermidine above 125 μM decreased the amount of intracellular hydrogen peroxide in a concentration-dependent manner in DCFH-DA analysis. It was also found that spermidine above 2000 μM increased melanin synthesis in living cells. However, spermidine above 1000 μM increased melanin synthesis in a concentration-dependent manner in H2 O2 -treated B16F1 cells. Furthermore, spermidine enhanced the expression of tyrosine hydroxylase via MITF transcription factor involved in melanogenesis in H2 O2 -treated B16F1 cells. Therefore, these results suggest that spermidine could be applied as a potential stimulator of melanin synthesis for the prevention of hair greying.

Keywords: MITF; melanin; spermidine; tyrosine hydroxylase; α-MSH.

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Biphenyl Compounds / antagonists & inhibitors
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Hydrogen Peroxide / antagonists & inhibitors
  • Hydrogen Peroxide / metabolism
  • Melanins / biosynthesis*
  • Mice
  • Microphthalmia-Associated Transcription Factor / genetics
  • Microphthalmia-Associated Transcription Factor / metabolism*
  • Picrates / antagonists & inhibitors
  • Spermidine / pharmacology*
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Antioxidants
  • Biphenyl Compounds
  • Melanins
  • Microphthalmia-Associated Transcription Factor
  • Mitf protein, mouse
  • Picrates
  • Hydrogen Peroxide
  • 1,1-diphenyl-2-picrylhydrazyl
  • Spermidine