Inhibition of melanogenesis by tyrosinase siRNA in human melanocytes

  • An, Sang-Mi (Department of Molecular Medicine and Cell and Matrix Research Institute, BK21 Medical Education Program for Human Resources, Kyungpook National University School of Medicine) ;
  • Koh, Jae-Sook (Dermapro) ;
  • Boo, Yong-Chool (Department of Molecular Medicine and Cell and Matrix Research Institute, BK21 Medical Education Program for Human Resources, Kyungpook National University School of Medicine)
  • 발행 : 2009.03.31


Tyrosinase (TYR) plays a critical role in cellular melanogenesis and, thus, has been the major target of pharmacological approaches for the control of skin pigmentation. This study examined an alternative molecular approach using TYR-small interfering RNA (siRNA) to control melanogenesis in the human melanocytes. Both the mRNA and protein levels of TYR were significantly lowered by TYR-siRNA treatment, whereas TYR-related protein 1 and TYR-related protein 2 displayed no such changes. TYR-siRNA treatment inhibited the cellular melanin synthesis from the externally supplied TYR substrate L-tyrosine. TYR-siRNA also suppressed melanin synthesis and decreased the viability of cells exposed to ultraviolet radiation, supporting a critical role of melanin in protection against ultraviolet radiation. These results suggest that molecular approaches using siRNA targeted to the enzymes of melanogenic pathway may provide a novel strategy for the control of cell pigmentation.


  1. Slominski, A. (2002) Coming of age of melanogenesis-related proteins. Arch. Pathol. Lab. Med. 126, 775-777
  2. Solano, F., Briganti, S., Picardo, M. and Ghanem, G. (2006) Hypopigmenting agents: an updated review on biological, chemical and clinical aspects. Pigment. Cell Res. 19, 550-571
  3. Parvez, S., Kang, M., Chung, H. S., Cho, C., Hong, M. C., Shin, M. K. and Bae, H. (2006) Survey and mechanism of skin depigmenting and lightening agents. Phytother. Res. 20, 921-934
  4. An, S. M., Lee, S. I., Choi, S. W., Moon, S. W. and Boo, Y. C. (2008) p-Coumaric acid, a constituent of Sasa quelpaertensis Nakai, inhibits cellular melanogenesis stimulated by alpha-melanocyte stimulating hormone. Br. J. Dermatol. 159, 292-299
  5. Kim, H. J., An, S. M. and Boo, Y. C. (2008) A dual mechanism of 4-hydroxy-5-methyl-3[2H]-furanone inhibiting cellular melanogenesis. J. Cosmet. Sci. 59, 117-125
  6. Kim, H. J., An, S. M. and Boo, Y. C. (2008) A dual mechanism of 4-hydroxy-5-methyl-3[2H]-furanone inhibiting cellular melanogenesis. J. Cosmet. Sci. 59, 117-125
  7. An, S. M., Kim, H. J., Kim, J. E. and Boo, Y. C. (2008) Flavonoids, taxifolin and luteolin attenuate cellular melanogenesis despite increasing tyrosinase protein levels. Phytother. Res. 22, 1200-1207
  8. Wickelgren, I. (2007) Skin biology. A healthy tan? Science 315, 1214-1216
  9. D'Orazio, J. A., Nobuhisa, T., Cui, R., Arya, M., Spry, M., Wakamatsu, K., Igras, V., Kunisada, T., Granter, S. R., Nishimura, E. K., Ito, S. and Fisher, D. E. (2006) Topical drug rescue strategy and skin protection based on the role of Mc1r in UV-induced tanning. Nature 443, 340-344
  10. Yamaguchi, Y., Beer, J. Z. and Hearing, V. J. (2008) Melanin mediated apoptosis of epidermal cells damaged by ultraviolet radiation: factors influencing the incidence of skin cancer. Arch. Dermatol. Res. 300(Suppl. 1), S43-50
  11. Iwata, M., Corn, T., Iwata, S., Everett, M. A. and Fuller, B. B. (1990) The relationship between tyrosinase activity and skin color in human foreskins. J. Invest. Dermatol. 95, 9-15
  12. Iozumi, K., Hoganson, G. E., Pennella, R., Everett, M. A. and Fuller, B. B. (1993) Role of tyrosinase as the determinant of pigmentation in cultured human melanocytes. J. Invest. Dermatol. 100, 806-811
  13. Fire, A., Xu, S., Montgomery, M. K., Kostas, S. A., Driver, S. E. and Mello, C. C. (1998) Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391, 806-811
  14. Kim, J., Kim, H., Lee, Y., Yang, K., Byun, S. and Han, K. (2006) A simple and economical short-oligonucleotidebased approach to shRNA generation. J. Biochem. Mol. Biol. 39, 329-334
  15. Hammond, S. M., Bernstein, E., Beach, D. and Hannon, G. J. (2000) An RNA-directed nuclease mediates post-transcriptional gene silencing in Drosophila cells. Nature 404, 293-296
  16. Mun, G. I., An, S. M., Park, H., Jo, H. and Boo, Y. C. (2008) Laminar shear stress inhibits lipid peroxidation induced by high glucose plus arachidonic acid in endothelial cells. Am. J. Physiol. Heart Circ. Physiol. 295, 1966-1973
  17. Nakai, N., Kishida, T., Shin-Ya, M., Imanishi, J., Ueda, Y., Kishimoto, S. and Mazda, O. (2007) Therapeutic RNA interference of malignant melanoma by electrotransfer of small interfering RNA targeting Mitf. Gene. Ther. 14, 357-365
  18. Boonanuntanasarn, S., Yoshizaki, G. and Takeuchi, T. (2003) Specific gene silencing using small interfering RNAs in fish embryos. Biochem. Biophys. Res. Commun. 310, 1089-1095
  19. Busca, R. and Ballotti, R. (2000) Cyclic AMP a key messenger in the regulation of skin pigmentation. Pigment. Cell Res. 13, 60-69
  20. Slominski, A., Wortsman, J., Luger, T., Paus, R. and Solomon, S. (2000) Corticotropin releasing hormone and proopiomelanocortin involvement in the cutaneous response to stress. Physiol. Rev. 80, 979-1020
  21. Steinhoff, M., St$\ddot{a}$nder, S., Seeliger, S., Ansel, J. C., Schmelz, M. and Luger, T. (2003) Modern aspects of cutaneous neurogenic inflammation. Arch. Dermatol. 139, 1479-1488
  22. Mas, J. S., Gerritsen, I., Hahmann, C., Jimenez-Cervantes, C. and Garcia-Borron, J. C. (2003) Rate limiting factors in melanocortin 1 receptor signalling through the cAMP pathway. Pigment. Cell Res. 16, 540-547
  23. Yasumoto, K., Yokoyama, K., Takahashi, K., Tomita, Y. and Shibahara, S. (1997) Functional analysis of microphthalmia- associated transcription factor in pigment cell-specific transcription of the human tyrosinase family genes. J. Biol. Chem. 272, 503-509
  24. Rozen, S. and Skaletsky, H. (2000) Primer3 on the WWW for general users and for biologist programmers. Methods Mol. Biol. 132, 365-386

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