title: Glycyrrhizin induces melanogenesis by elevating a cAMP level in b16 melanoma cells.
abstract: In mammalian melanocytes, melanin synthesis is controlled by tyrosinase, the critical enzyme in the melanogenic pathway. A recent report showed that the stimulation of melanogenesis by glycyrrhizin (GR) is because of an increased tyrosinase expression at mRNA and protein levels. But, the molecular events of melanogenesis induced by GR remain to be elucidated. In this study, using B16 melanoma cells, we showed that GR activated activator protein-1 (AP-1) and cyclic response filament "CRE" promoters, but not the nuclear factor-kappaB promoter. In addition, although GR stimulated mitogen-activated protein (MAP) kinase, p42/44(mapk), consistent with GR-induced AP-1 promoter activation, GR-induced melanogenesis was not blocked by PD98059, an MEK1 inhibitor, suggesting that MAPkinase induced by GR does not have a direct effect on the level of melanin content. But, GR-induced melanogenesis was inhibited by an inhibitor of protein kinase A (H-89). This result was further confirmed by the fact that GR induced the phosphorylation of CRE binding protein (CREB) and inhibition of glycogen synthase kinase 3beta phosphorylation as well as the production of cAMP, indicating that GR induces melanogenesis through cAMP signaling. In addition, the fact that GR-induced CRE activation was blocked by H-89 but GR-induced increase of cAMP production was not suggests that GR operates upstream of protein kinase A.
authors.affiliation: Biospectrum Life Science Institute, 101-107 SK Ventium, Dangjung-Dong, Kumpo-City, 435-776, Kyunggi-do, Korea.
authors.forename: Jongsung
authors.initials: J
authors.lastname: Lee
authors.forename: Eunsun
authors.initials: E
authors.lastname: Jung
authors.forename: Junho
authors.initials: J
authors.lastname: Park
authors.forename: Kwangseon
authors.initials: K
authors.lastname: Jung
authors.forename: Eunkyung
authors.initials: E
authors.lastname: Park
authors.forename: Jieun
authors.initials: J
authors.lastname: Kim
authors.forename: Sungtaek
authors.initials: S
authors.lastname: Hong
authors.forename: Jinil
authors.initials: J
authors.lastname: Park
authors.forename: Sanghee
authors.initials: S
authors.lastname: Park
authors.forename: Sangyeop
authors.initials: S
authors.lastname: Lee
authors.forename: Deokhoon
authors.initials: D
authors.lastname: Park
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D019695:Glycyrrhizic Acid / Q000494:pharmacology*; D048728:MAP Kinase Kinase Kinase 1 / Q000378:metabolism; D008543:Melanins / Q000378:metabolism; D008544:Melanocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008545:Melanoma; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D014442:Monophenol Monooxygenase / Q000235:genetics; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011401:Promoter Regions, Genetic; D015398:Signal Transduction / Q000187:drug effects; D012878:Skin Neoplasms; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014407:Tumor Cells, Cultured; D018631:ras Proteins / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D017362:Cyclic AMP Response Element-Binding Protein; D008543:Melanins; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D019695:Glycyrrhizic Acid; D000242:Cyclic AMP; D014442:Monophenol Monooxygenase; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048728:MAP Kinase Kinase Kinase 1; D038362:Glycogen Synthase Kinase 3; D018631:ras Proteins