The effects of Caffeoylserotonin on inhibition of melanogenesis through the downregulation of MITF via the reduction of intracellular cAMP and acceleration of ERK activation in B16 murine melanoma cells
2
조회
0
다운로드
4
인용
0
참고문헌
키워드
초록
In this study, we evaluated the anti-melanogenesis effects of Caffeoylserotonin (CaS) in B16 melanoma cells. Treatment with CaS reduced the melanin content and tyrosinase (TYR) activity in B16 melanoma cells in a dose-dependent manner. CaS inhibited the expression of melanogenesis-related proteins, including microphthalmia-associated transcription factor (MITF), TYR, and tyrosinase-related protein-1 (TRP-1), but not TRP-2. α-MSH is known to interact with melanocortin 1 receptor (MC1R) thus activating adenylyl cyclase and increasing intracellular cyclic AMP (cAMP) levels. Furthermore, cAMP activates extracellular signal-regulated kinase 2 (ERK2) via phosphorylation, which phosphorylates MITF, thereby targeting the transcription factor to proteasomes for degradation. The CaS reduced intracellular cAMP levels to unstimulated levels and activated ERK phosphorylation within 30 min. The ERK inhibitor PD98059 abrogated the suppressive effect of CaS on α-MSH-induced melanogenesis. Based on this study, the inhibitory effects of CaS on melanogenesis are derived from the downregulation of MITF signaling via the inhibition of intracellular cAMP levels, as well as acceleration of ERK activation. [BMB Reports 2012; 45(12): 724-729]
Abstract
In this study, we evaluated the anti-melanogenesis effects of Caffeoylserotonin (CaS) in B16 melanoma cells. Treatment with CaS reduced the melanin content and tyrosinase (TYR) activity in B16 melanoma cells in a dose-dependent manner. CaS inhibited the expression of melanogenesis-related proteins, including microphthalmia-associated transcription factor (MITF), TYR, and tyrosinase-related protein-1 (TRP-1), but not TRP-2. α-MSH is known to interact with melanocortin 1 receptor (MC1R) thus activating adenylyl cyclase and increasing intracellular cyclic AMP (cAMP) levels. Furthermore, cAMP activates extracellular signal-regulated kinase 2 (ERK2) via phosphorylation, which phosphorylates MITF, thereby targeting the transcription factor to proteasomes for degradation. The CaS reduced intracellular cAMP levels to unstimulated levels and activated ERK phosphorylation within 30 min. The ERK inhibitor PD98059 abrogated the suppressive effect of CaS on α-MSH-induced melanogenesis. Based on this study, the inhibitory effects of CaS on melanogenesis are derived from the downregulation of MITF signaling via the inhibition of intracellular cAMP levels, as well as acceleration of ERK activation. [BMB Reports 2012; 45(12): 724-729]
참고문헌 (20)
- Marmol, V., "Tyrosinase and related proteins in mammalian pigmentation", FEBS Lett., 381, pp.165~168 (1996)
- Young-Sang Lee, "Inhibitory effect of glyceollin isolated from soybean against melanogenesis in B16 melanoma cells", BMB Reports, 43(7), pp.461~467 (2010), 생화학분자생물학회
- Sun Young Park, "Beta-carboline alkaloids harmaline and harmalol induce melanogenesis through p38 mitogen-activated protein kinase in B16F10 mouse melanoma cells", BMB Reports, 43(12), pp.824~829 (2010), 생화학분자생물학회
- Gaggioli, C., "Microphthalmia-associated transcription factor (MITF) is required but is not sufficient to induce the expression of melanogenic genes", Pigment. Cell Res., 16, pp.374~382 (2003)
- Buscà, R., "Cyclic AMP a key messenger in the regulation of skin pigmentation", Pigment. Cell Res., 12, pp.60~69 (2000)
- Bertolotto, C., "Microphtalmia gene product as a signal transducer in cAMP-induced differentiation of melanocytes", J. Cell Biol., 142, pp.827~835 (1998)
- Jang, J., "Dichloromethan fraction of Cimicifuga heracleifoliadecreases the level of melanin synthesis by activatingthe ERK or Akt signaling pathway in B16F10 cells", Exp. Dermatol., 18, pp.232~237 (2009)
- Englaro, W., "Inhibition of the mitogen-activated protein kinase pathway triggers B16 melanoma cell differentiation", J. Biol. Chem., 273, pp.9966~9970 (1998)
- Kang, K., "Biosynthesis and biotechnological production of serotonin derivatives", Appl. Microbiol. Biotechno., 8, pp.27~34 (2009)
- Tanaka, E., "Phenylpropanoid amides of serotonin accumulate in witches’ broom diseased bamboo", Phytochemistry, 64, pp.965~969 (2003)
- Zhang, H. L., "Novel antioxidant from safflower (Carthamus tinctorius L.) oil cake", Chem. Pharm. Bull., 44, pp.874~876 (1996)
- Choi, J., "Cytoprotective activities of hydroxycinnamic acid amides of serotonin against oxidative stress-induced damage in HepG2 and HaCaT cells", FITOTERAPIA, 81, pp.1134~1141 (2010), ELSEVIER SCIENCE BV
- serotonins as potent inhibitors of tyrosinase from mouse and human melanoma cells, "Bioorg. Med. Chem. Lett.", 2009, 4178~4182
- Rouzaud, F., "MC1R and the response of melanocytes to ultraviolet radiation", Mutat. Res., 571, pp.133~152 (2005)
- Slominski, A., "Melanin pigmentation in mammalian skin and itshormonal regulation", Physiol. Rev., 84, pp.1155~1228 (2004)
- Price, E. R., "Lineage-specific signaling in melanocytes. C-kit stimulation recruits p300", CBP to microphthalmia, 1998, pp.273, 17983~17986
- Wu, W., "c-Kit triggers dual phosphorylations, which couple activation and degradation of the essential melanocyte factor Mi", Genes. Dev., 14, pp.301~312 (2000)
- Kim, H., "Anti-inflammatory activity of a water extract of Acorus calamus L. leaves on keratinocyte HaCaT cells", J. Ethnopharmacol., 17, pp.133~138 (2009)
- Tsuboi, T., "Enhanced melanogenesis induced by tyrosinasegene-transfer increases boron-uptake and killing effect ofboron neutron capture therapy for amelanotic melanoma", Pigment Cell Res., 11, pp.275~282 (1998)
- Takahashi, H., "Rapid and reversible inhibition of tyrosinase activity by glucosidase inhibitors in human melanoma cells", J. Invest. Dermatol., 98, pp.481~487 (1992)