title: Effect of pyrroloquinoline quinone (PQQ) on melanogenic protein expression in murine B16 melanoma.
abstract: BACKGROUND
  Increased production and accumulation of melanin leads to various hyperpigmentation disorders. Melanin synthesis is regulated by melanogenic proteins such as tyrosinase, tyrosinase-related protein (TRP)-1 and -2, and their transcription factors.
  
  
  OBJECTIVE
  In this study, we assessed the effects of PQQ on melanogenic protein expression of murine B16 melanoma cells.
  
  
  METHODS
  We assessed melanin production of PQQ-treated B16 melanoma cells. Furthermore, we investigated the effect of PQQ on the activity of melanogenic enzymes and their expression using Western blot and semi-quantitative RT-PCR analyses.
  
  
  RESULTS
  In the present study, PQQ inhibited melanin synthesis in cultured melanoma cells stimulated by either alpha-melanocyte stimulating hormone (alpha-MSH) or 3-isobutyl-1-methylxanthine (IBMX). To elucidate the mechanism of the effect of PQQ on melanogenesis, we performed Western blotting for melanogenic proteins, such as tyrosinase, TRP-1, and TRP-2. PQQ inhibited tyrosinase expression, however, it did not inhibit TRP-2 expression. Used as the stimulant for melanogenesis, both alpha-MSH and IBMX gave the same results for melanogenic protein expression. Semi-quantitative RT-PCR analysis showed that the depigmentation effect of PQQ might be due to the inhibition of tyrosinase gene transcription but not the inhibition of microphthalmia-associated transcription factor (Mitf).
  
  
  CONCLUSIONS
  This report indicates that PQQ is a possible anti-melanogenic agent and might be effective against hyperpigmentation disorders.
authors.affiliation: Department of Applied Biological Chemistry, Faculty of Agriculture, Shizuoka University, 836 Ohya, Shizuoka, 422-8529, Japan. w6611007@ipc.shizuoka.ac.jp
authors.forename: Kazuomi
authors.initials: K
authors.lastname: Sato
authors.forename: Masaru
authors.initials: M
authors.lastname: Toriyama
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D008543:Melanins / Q000096:biosynthesis*; D008546:Melanoma, Experimental / Q000201:enzymology* / Q000235:genetics; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor / Q000378:metabolism; D014442:Monophenol Monooxygenase / Q000235:genetics / Q000378:metabolism*; D010088:Oxidoreductases / Q000378:metabolism; D045542:PQQ Cofactor / Q000494:pharmacology*; D010858:Pigmentation / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D000521:alpha-MSH / Q000378:metabolism
chemical_list: D008543:Melanins; D008562:Membrane Glycoproteins; D051739:Microphthalmia-Associated Transcription Factor; C497235:Mitf protein, mouse; D012333:RNA, Messenger; D000521:alpha-MSH; D045542:PQQ Cofactor; D010088:Oxidoreductases; C079621:Tyrp1 protein, mouse; D014442:Monophenol Monooxygenase; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase; D015056:1-Methyl-3-isobutylxanthine