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Downregulation of NFAT2 promotes melanogenesis in B16 melanoma cells

  • Lee, Young-Sook (Department of Anatomy, School of Medicine, Chungnam National University) ;
  • Kim, Dong-Woon (Department of Anatomy, School of Medicine, Chungnam National University) ;
  • Kim, Soo-Il (Department of Anatomy, School of Medicine, Chungnam National University) ;
  • Choi, Hye-In (Department of Anatomy, School of Medicine, Chungnam National University) ;
  • Lee, Young (Department of Dermatology, School of Medicine, Chungnam National University) ;
  • Kim, Chang-Deok (Department of Dermatology, School of Medicine, Chungnam National University) ;
  • Lee, Jeung-Hoon (Department of Dermatology, School of Medicine, Chungnam National University) ;
  • Lee, Sang-Do (Department of Physiology, School of Medicine, Chungnam National University) ;
  • Lee, Young-Ho (Department of Anatomy, School of Medicine, Chungnam National University)
  • Received : 2010.11.16
  • Accepted : 2010.12.03
  • Published : 2010.12.30

Abstract

Nuclear factor of activated T-cells (NFAT) proteins are, calcium-regulated transcription factors, key regulator of stimulation-dependent gene activation. In our microarray analysis for the genes expressed in human black and white hairs, NFAT2 was significantly upregulated in the white hair, compared to the black hair. The aim of this study was to investigate functional role of NFAT2 in melanogenesis. Western blot analysis was performed to investigate the expression of NFAT2 protein in B16 melanoma cells. Our data showed that NFAT2 expression was increased in the hypopigmented B16 cells, while tyrosinase and MITF expression was decreased. To investigate the potential role of NFAT2, the recombinant adenovirus expressing microRNA specific for NFAT2 was transduced into the cultured B16 melanoma cells. Consistently, inhibition of NFAT2 enhanced tyrosinase activity and melanin content. Moreover, cyclosporine A, which is known as a calcineurin inhibitor blocking NFAT activation, enhanced tyrosinase activity and melanin content. These data suggest that NFAT2 may play an important role in regulation of melanogenesis in melanocyte.

Keywords

Acknowledgement

Supported by : Chungnam National University

References

  1. Al-Daraji WI, Afolayan J, Zelger BG, Abdellaoui A, Zelger B. (2009). Modulation of NFAT-5, an outlying member of the NFAT family, in human keratinocytes and skin. Am J Transl Res 1: 184-202
  2. Costin GE, Hearing VJ. (2007). Human skin pigmentation: melanocytes modulate skin color in response to stress. FASEB J 21: 976-994 https://doi.org/10.1096/fj.06-6649rev
  3. Flockhart RJ, Armstrong JL, Reynolds NJ, Lovat PE. (2009). NFAT signalling is a novel target of oncogenic BRAF in metastatic melanoma. Br J Cancer 101: 1448-1455 https://doi.org/10.1038/sj.bjc.6605277
  4. Flockhart RJ, Diffey BL, Farr PM, Lloyd J, Reynolds NJ. (2008). NFAT regulates induction of COX-2 and apoptosis of keratinocytes in response to ultraviolet radiation exposure. FASEB J 22: 4218-4227 https://doi.org/10.1096/fj.08-113076
  5. Friedmann PS, Wren FE, Matthews JN. (1990). Ultraviolet stimulated melanogenesis by human melanocytes is augmented by di-acyl glycerol but not TPA. J Cell Physiol 142: 334-341 https://doi.org/10.1002/jcp.1041420216
  6. Fung-Leung WP, Pope BL, Chourmouzis E, Panakos JA, Lau CY. (1995). Tepoxalin, a novel immunomodulatory compound, synergizes with CsA in suppression of graft-versus-host reaction and allogeneic skin graft rejection. Transplantation 60: 362-368 https://doi.org/10.1097/00007890-199508270-00011
  7. Gafter-Gvili A, Sredni B, Gal R, Gafter U, Kalechman Y. (2003). Cyclosporin A-induced hair growth in mice is associated with inhibition of calcineurin-dependent activation of NFAT in follicular keratinocytes. Am J Physiol Cell Physiol 284: C1593-C1603 https://doi.org/10.1152/ajpcell.00537.2002
  8. Gauthier M, Degnan BM. (2008). The transcription factor NF-kappaB in the demosponge Amphimedon queenslandica: insights on the evolutionary origin of the Rel homology domain. Dev Genes Evol 218: 23-32 https://doi.org/10.1007/s00427-007-0197-5
  9. Horsley V, Aliprantis AO, Polak L, Glimcher LH, Fuchs E. (2008). NFATc1 balances quiescence and proliferation of skin stem cells. Cell 132: 299-310 https://doi.org/10.1016/j.cell.2007.11.047
  10. Hunt G, Todd C, Cresswell JE, Thody AJ. (1994). Alpha-melanocyte stimulating hormone and its analogue Nle4DPhe7 alpha-MSH affect morphology, tyrosinase activity and melanogenesis in cultured human melanocytes. J Cell Sci 107: 205-211
  11. Kadekaro AL, Wakamatsu K, Ito S, Abdel-Malek ZA. (2006). Cutaneous photoprotection and melanoma susceptibility: reaching beyond melanin content to the frontiers of DNA repair. Front Biosci 11: 2157-2173 https://doi.org/10.2741/1958
  12. Kuo CT, Leiden JM. (1999). Transcriptional regulation of T lymphocyte development and function. Annu Rev Immunol 17: 149-187 https://doi.org/10.1146/annurev.immunol.17.1.149
  13. Macian F, Lopez-Rodriguez C, Rao A. (2001). Partners in transcription: NFAT and AP-1. Oncogene 20: 2476-2489 https://doi.org/10.1038/sj.onc.1204386
  14. Maeda K, Yokokawa Y, Hatao M, Naganuma M, Tomita Y. (1997). Comparison of the melanogenesis in human black and light brown melanocytes. J Dermatol Sci 14: 199-206 https://doi.org/10.1016/S0923-1811(96)00575-0
  15. Mammucari C, Tommasi di Vignano A, Sharov AA, et al. (2005). Integration of Notch 1 and calcineurin/NFAT signaling pathways in keratinocyte growth and differentiation control. Dev Cell 8: 665-676 https://doi.org/10.1016/j.devcel.2005.02.016
  16. Murakami M, Matsuzaki F, Funaba M. (2009). Regulation of melanin synthesis by the TGF-beta family in B16 melanoma cells. Mol Biol Rep 36: 1247-1250 https://doi.org/10.1007/s11033-008-9304-6
  17. Na IK, Markley JC, Tsai JJ, et al. (2010). Concurrent visualization of trafficking, expansion, and activation of T lymphocytes and T-cell precursors in vivo. Blood 116: e18-e25 https://doi.org/10.1182/blood-2009-12-259432
  18. Oh-hora M. (2009). Calcium signaling in the development and function of T-lineage cells. Immunol Rev 231: 210-224 https://doi.org/10.1111/j.1600-065X.2009.00819.x
  19. Ouyang W, Hu Y, Li J, et al. (2007). Direct evidence for the critical role of NFAT3 in benzo[a]pyrene diol-epoxide-induced cell transformation through mediation of inflammatory cytokine TNF induction in mouse epidermal Cl41 cells. Carcinogenesis 28: 2218-2226 https://doi.org/10.1093/carcin/bgm115
  20. Pores-Fernando AT, Zweifach A. (2009). Calcium influx and signaling in cytotoxic T-lymphocyte lytic granule exocytosis. Immunol Rev 231: 160-173 https://doi.org/10.1111/j.1600-065X.2009.00809.x
  21. Rinne A, Banach K, Blatter LA. (2009). Regulation of nuclear factor of activated T cells (NFAT) in vascular endothelial cells. J Mol Cell Cardiol 47: 400-410 https://doi.org/10.1016/j.yjmcc.2009.06.010
  22. Romero-Graillet C, Aberdam E, Biagoli N, Massabni W, Ortonne JP, Ballotti R. (1996). Ultraviolet B radiation acts through the nitric oxide and cGMP signal transduction pathway to stimulate melanogenesis in human melanocytes. J Biol Chem 271: 28052-28056 https://doi.org/10.1074/jbc.271.45.28052
  23. Santini MP, Talora C, Seki T, Bolgan L, Dotto GP. (2001). Cross talk among calcineurin, Sp1/Sp3, and NFAT in control of p21(WAF1/CIP1) expression in keratinocyte differentiation. Proc Natl Acad Sci U S A 98: 9575-9580 https://doi.org/10.1073/pnas.161299698
  24. Sawada M, Terada N, Taniguchi H, Tateishi R, Mori Y. (1987). Cyclosporin A stimulates hair growth in nude mice. Lab Invest 56: 684-686
  25. Shibahara S, Yasumoto K, Amae S, et al. (2000). Regulation of pigment cell-specific gene expression by MITF. Pigment Cell Res 13(Suppl 8): 98-102 https://doi.org/10.1034/j.1600-0749.13.s8.18.x
  26. Wolfe SA, Zhou P, DÖtsch V, et al. (1997). Unusual Rel-like architecture in the DNA-binding domain of the transcription factor NFATc. Nature 385: 172-176 https://doi.org/10.1038/385172a0
  27. Wu X, Nguyen BC, Dziunycz P, et al. (2010). Opposing roles for calcineurin and ATF3 in squamous skin cancer. Nature 465: 368-372 https://doi.org/10.1038/nature08996

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