title: Glycine hydroxamate inhibits tyrosinase activity and melanin contents through downregulating cAMP/PKA signaling pathways.
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.
authors.affiliation: Graduate Institute of Pharmacognosy, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yin-Shiou
authors.initials: YS
authors.lastname: Lin
authors.forename: Wen-Chung
authors.initials: WC
authors.lastname: Wu
authors.forename: Shyr-Yi
authors.initials: SY
authors.lastname: Lin
authors.forename: Wen-Chi
authors.initials: WC
authors.lastname: Hou
mesh_terms: D045744:Cell Line, Tumor; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005998:Glycine / Q000494:pharmacology; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D008543:Melanins / Q000096:biosynthesis*; D051739:Microphthalmia-Associated Transcription Factor / Q000378:metabolism; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015290:Second Messenger Systems / Q000187:drug effects*; D014357:Trypsin / Q000378:metabolism; D000521:alpha-MSH / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; C497234:MITF protein, human; D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; D000521:alpha-MSH; D000242:Cyclic AMP; D014442:Monophenol Monooxygenase; D017868:Cyclic AMP-Dependent Protein Kinases; C489303:PRSS1 protein, human; D014357:Trypsin; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase; D005998:Glycine