Agmatine modulates melanogenesis via MITF signaling pathway

Environ Toxicol Pharmacol. 2017 Jan:49:124-130. doi: 10.1016/j.etap.2016.12.008. Epub 2016 Dec 13.

Abstract

Agmatine contained in soybean is also found in Manaca, an anti-aging plant, inhabited in Amazon and induces vasodilation by the promotion of NO synthesis in blood vessel. However, the research of agmatine on melanin synthesis related to hair greying is lacking. The aim of this study was to investigate the melanogenic effect of agmatine via regulation of MITF signaling pathway in B16F1 cells. It was determined whether agmatine regulates melanin synthesis at cellular level in addition to the effect of agmatine on mushroom tyrosinase in vitro in the presence of different concentrations of agmatine. Furthermore, the effect of agmatine on the protein expressions of tyrosinase, TRP-1, TRP-2, BMP-4, BMP-6, C-KIT, p-p38, MITF and C-FOS were examined by western blot analysis. In addition, immunofluorescence staining was carried out to visualize the location of MITF expression in cell. Agmatine at 256μM or more increased melanin synthesis as well as tyrosinase activity. Moreover, whereas agmatine increased the expression levels of TRP-1, BMP-6, p-p38 and MITF, it reduced the expression level of BMP-4. It was also found that agmatine enhanced the expression level of MITF in nucleus. These results suggest that agmatine could induce melanin synthesis though the regulation of MITF transcription factor via BMP-6/p38 signaling pathway.

Keywords: Agmatine; BMP-6; MITF; Melanin synthesis; p38.

MeSH terms

  • Agmatine / pharmacology*
  • Animals
  • Bone Morphogenetic Protein 4 / metabolism
  • Bone Morphogenetic Protein 6 / metabolism
  • Cell Line, Tumor
  • Intramolecular Oxidoreductases / metabolism
  • Melanins / biosynthesis*
  • Mice
  • Microphthalmia-Associated Transcription Factor / metabolism*
  • Monophenol Monooxygenase / metabolism
  • Oxidoreductases / metabolism
  • Proto-Oncogene Proteins c-fos / metabolism
  • Proto-Oncogene Proteins c-kit / metabolism
  • Signal Transduction / drug effects
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Bone Morphogenetic Protein 4
  • Bone Morphogenetic Protein 6
  • Melanins
  • Microphthalmia-Associated Transcription Factor
  • Proto-Oncogene Proteins c-fos
  • Agmatine
  • Oxidoreductases
  • tyrosinase-related protein-1
  • Monophenol Monooxygenase
  • Proto-Oncogene Proteins c-kit
  • p38 Mitogen-Activated Protein Kinases
  • Intramolecular Oxidoreductases
  • dopachrome isomerase