Effect of pyrroloquinoline quinone (PQQ) on melanogenic protein expression in murine B16 melanoma.
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.
Sato
Kazuomi
K
Department of Applied Biological Chemistry, Faculty of Agriculture, Shizuoka University, 836 Ohya, Shizuoka, 422-8529, Japan. w6611007@ipc.shizuoka.ac.jp
Toriyama
Masaru
M
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
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