Glycine hydroxamate inhibits tyrosinase activity and melanin contents through downregulating cAMP/PKA signaling pathways

Amino Acids. 2015 Mar;47(3):617-25. doi: 10.1007/s00726-014-1895-8. Epub 2014 Dec 16.

Abstract

Among the eight amino acid hydroxamates tested, Glycine hydroxamate (GH) was the best inhibitor of mushroom tyrosinase (TYR). With L-tyrosine as substrate, the GH inhibition of the monophenolase activity of the mushroom TYR was noncompetitive. GH decreased not only TYR protein expression, but also melanin content, tyrosinase-related protein (TRP)-1, TRP-2, and microphthalmia-associated transcription factor (MITF) expression in B16F10 melanoma cells while in the presence of α-melanocyte-stimulating hormone (α-MSH). GH also significantly decreased the isobutylmethylxanthine (IBMX)-induced increase in melanin content, which was not prevented by the ERK inhibitor PD98059. These results suggest GH has the potential for use in cosmetic hypopigmentation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cyclic AMP / metabolism*
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Enzyme Inhibitors / pharmacology*
  • Glycine / pharmacology
  • Humans
  • Hydroxamic Acids / pharmacology
  • Intramolecular Oxidoreductases / metabolism
  • Melanins / biosynthesis*
  • Microphthalmia-Associated Transcription Factor / metabolism
  • Monophenol Monooxygenase / antagonists & inhibitors*
  • Monophenol Monooxygenase / metabolism
  • Second Messenger Systems / drug effects*
  • Trypsin / metabolism
  • alpha-MSH / pharmacology

Substances

  • Enzyme Inhibitors
  • Hydroxamic Acids
  • MITF protein, human
  • Melanins
  • Microphthalmia-Associated Transcription Factor
  • alpha-MSH
  • Cyclic AMP
  • Monophenol Monooxygenase
  • Cyclic AMP-Dependent Protein Kinases
  • PRSS1 protein, human
  • Trypsin
  • Intramolecular Oxidoreductases
  • dopachrome isomerase
  • Glycine