Sphigosine-1-Phosphate-Induced ERK Activation Protects Human Melanocytes from UVB-Induced Apoptosis

  • Kim, Dong-Seok (Research Division for Human Life Sciences, Seoul National University, Department of Dermatology, Seoul National University College of Medicine) ;
  • Kim, Sook-Young (Department of Dermatology, Seoul National University College of Medicine) ;
  • Lee, Jai-Eun (Department of Dermatology, Seoul National University College of Medicine) ;
  • Kwon, Sun-Bang (Department of Dermatology, Seoul National University College of Medicine) ;
  • Joo, Young-Hyun (Department of Dermatology, Seoul National University College of Medicine) ;
  • Youn, Sang-Woong (Department of Dermatology, Seoul National University College of Medicine) ;
  • Park, Kyoung-Chan (Department of Dermatology, Seoul National University College of Medicine)
  • Published : 2003.09.01

Abstract

Ultraviolet B (UVB) is known to induce apoptosis in human melanocytes. Here we show the cytoprotective effect of sphingosine-1-phosphate (S1P) against UVB-induced apoptosis. We also show that UVB-induced apoptosis of melanocytes is mediated by caspase-3 activation and poly(ADP-ribose) polymerase (PARP) cleavage, and that S1P prevents apoptosis by inhibiting this apoptotic pathway. We further investigated three major mitogen-activated protein (MAP) kinases after UVB irradiation. UVB gradually activated c-Jun N-terminal kinase (JNK) and p38 MAP kinase, while extracellular signal-regulated protein kinase (ERK) was inactivated transiently. Blocking of the p38 MAP kinase pathway using SB203580 promoted cell survival and inhibited the activation of caspase-3 and PARP cleavage. These results suggest that p38 MAP kinase activation may play an important role in the UVB-induced apoptosis of human melanocytes. To explain this cytoprotective effect, we next examined whether S1P could inhibit UVB-induced JNK and p38 MAP kinase activation. However, S1P was not found to have any influence on UVB-induced JNK or p38 MAP kinase activation. In contrast, S1P clearly stimulated the phosphorylation of ERK, and the specific inhibition of the ERK pathway using PD98059 abolished the cytoprotective effect of S1P. Based on these results, we conclude that the activation of p38 MAP kinase plays an important role in UVB-induced apoptosis, and that S1P may show its cytoprotective effect through ERK activation in human melanocytes.

Keywords

References

  1. Bain, J., McLauchlan, H., Elliott, M., and Cohen, P., The specificities of protein kinase inhibitors: an update. Biochem J, 371, 199-204 (2003) https://doi.org/10.1042/BJ20021535
  2. Bennett, B. L., Sasaki, D. T., Murray, B. W., O'Leary, E. C., Sakata, S. T., Xu, W., Leisten, J. C., Motiwala, A., Pierce, S., Satoh, Y., Bhagwat, S. S., Manning, A. M., and Anderson, D. W., SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase. Proc. Natl. Acad. Sci. U.S.A., 98, 13681-6(2001) https://doi.org/10.1073/pnas.251194298
  3. Bevan, P., Insulin signalling. J. Cell Sci., 114, 1429-30 (2001)
  4. Butterfield, L., Storey, B., Maas, L.. and Heasley, L. E., c-Jun $NH_2$-terminal kinase regulation of the apoptotic response of small cell lung cancer cells to ultraviolet radiation. J. Biol. Chem., 272, 10110-10116 (1997) https://doi.org/10.1074/jbc.272.15.10110
  5. Chang, L. and Karin, M., Mammalian MAP kinase signalling cascades. Nature., 410, 37-40 (2001) https://doi.org/10.1038/35065000
  6. Cuvillier, O., Pirianov, G., Kleuser, B., Vanek, P. G., Coso, O. A., Gutkind, S., and Spiegel, S., Suppression of ceramide-mediated programmed cell death by sphingosine-1-phosphate. Nature, 381, 800-803 (1996) https://doi.org/10.1038/381800a0
  7. Cuvillier, O., Rosenthal, D. S., Smulson, M. E., and Spiegel, S., Sphingosine 1-phosphate inhibits activation of caspases that cleave poly(ADP-ribose) polymerase and lamins during Fasand ceramide-mediated apoptosis in Jurkat T lymphocytes. J. Biol. Chem., 273, 2910-2916 (1998) https://doi.org/10.1074/jbc.273.5.2910
  8. Dooley, T. P., Gadwood, R. C., Kilgore, K., and Thomasco, L. M., Development of an in vitro primary screen for skin depigmentation and antimelanoma agents. Skin Pharmacol., 7, 188-200 (1994) https://doi.org/10.1159/000211294
  9. Edsall, L. C., Cuvillier, O., Twitty, S., Spiegel, S., and Milstien, S., Sphingosine kinase expression regulates apoptosis and caspase activation in PC12 cells. J. Neurochem., 76, 1573-1584 (2001) https://doi.org/10.1046/j.1471-4159.2001.00164.x
  10. Edsall, L. C., Pirianov, G. G., and Spiegel, S., Involvement of sphingosine 1-phosphate in nerve growth factor-mediated neuronal survival and differentiation. J. Neurosci., 17, 6952-6960 (1997)
  11. Eisinger, M. and Marko, O., Selective proliferation of normal human melanocytes in vitro in the presence of phorbol ester and cholera toxin. Proc. Natl. Acad. Sci. U.S.A., 79, 2018-2022 (1982) https://doi.org/10.1073/pnas.79.6.2018
  12. Fischer, S. J., Podratz, J. L., and Windebank, A. J., Nerve growth factor rescue of cisplatin neurotoxicity is mediated through the high affinity receptor: studies in PC12 cells and p75 null mouse dorsal root ganglia. Neurosci. Lett., 308, 1-4 (2001) https://doi.org/10.1016/S0304-3940(01)01956-5
  13. Han, Z., Boyle, D. L., Chang, L., Bennett, B., Karin, M., Yang, L., Manning, A. M., and Firestein, G. S., c-Jun N-terminal kinase is required for metalloproteinase expression and joint destruction in inflammatory arthritis. J. Clin. Invest., 108, 73-81 (2001) https://doi.org/10.1172/JCI12466
  14. Harper, S. J. and LoGrasso, P., Signalling for survival and death in neurones: the role of stress-activated kinases, JNK and p38. Cell Signal, 13, 299-310 (2001) https://doi.org/10.1016/S0898-6568(01)00148-6
  15. Hengartner, M. O., The biochemistry of apoptosis. Nature., 407, 770-776 (2000) https://doi.org/10.1038/35037710
  16. Huang, C. L., Nordlund, J. J., and Boissy, R., Vitiligo: a manifestation of apoptosis? Am. J. Clin. Dermatol., 3, 301-308 (2002) https://doi.org/10.2165/00128071-200203050-00001
  17. Karliner, J. S., Honbo, N., Summers, K., Gray, M. O., and Goetzl, E. J., The lysophospholipids sphingosine-1-phosphate and lysophosphatidic acid enhance survival during hypoxia in neonatal rat cardiac myocytes. J. Mol. Cell Cardiol., 33, 1713-1717 (2001) https://doi.org/10.1006/jmcc.2001.1429
  18. Kim, D. S., Hwang, E. S., Lee, J. E., Kim, S. Y., Kwon, S. B., and Park, K. C., Sphingosine-1-phosphate decreases melanin synthesis via sustained ERK activation and subsequent MITF degradation. J. Cell Sci., 116, 1699-1706 (2003) https://doi.org/10.1242/jcs.00366
  19. Kim, Y. G., Kim, H. J., Kim, D. S., Kim, S. D., Han, W. S., Kim, K. H., Chung, J. H., and Park, K. C., Up-Regulation and redistribution of Bax in ultraviolet B-irradiated melanocytes. Pigment. Cell Res., 13, 352-357 (2000) https://doi.org/10.1034/j.1600-0749.2000.130508.x
  20. Kleuser, B., Cuvillier, O., and Spiegel, S., 1Alpha,25-dihydroxyvitamin D3 inhibits programmed cell death in HL-60 cells by activation of sphingosine kinase. Cancer Res., 58, 1817-1824 (1998)
  21. Kolch, W., Meaningful relationships: the regulation of the Ras/Raf/MEK/ERK pathway by protein interactions. Biochem. J. 351 Pt 2, 289-305 (2000) https://doi.org/10.1042/0264-6021:3510289
  22. Kwon, Y. G., Min, J. K., Kim, K. M., Lee, D. J., Billiar, T. R., and Kim, Y. M., Sphingosine 1-phosphate protects human umbilical vein endothelial cells from serum-deprived apoptosis by nitric oxide production. J. Biol. Chem., 276, 10627-10633 (2001) https://doi.org/10.1074/jbc.M011449200
  23. Manggau, M., Kim, D. S., Ruwisch, L., Vogler, R., Korting, H. C., Schafer-Korting, M., and Kleuser, B., 1Alpha,25-dihydroxy-vitamin D3 protects human keratinocytes from apoptosis by the formation of sphingosine-1-phosphate. J. Invest. Dermatol., 117, 1241-1249 (2001) https://doi.org/10.1046/j.0022-202x.2001.01496.x
  24. Marshall, C. J., Specificity of receptor tyrosine kinase signaling: transient versus sustained extracellular signal-regulated kinase activation. Cell, 80, 179-185 (1995) https://doi.org/10.1016/0092-8674(95)90401-8
  25. Medrano, E. E. and Nordlund, J. J., Successful culture of adult human melanocytes obtained from normal and vitiligo donors. J. Invest. Dermatol., 95, 441-445 (1990)
  26. Nava, V. E., Hobson, J. P., Murthy, S., Milstien, S., and Spiegel, S., Sphingosine kinase type 1 promotes estrogen-dependent tumorigenesis of breast cancer MCF-7 cells. Exp. Cell. Res., 281, 115-127 (2002) https://doi.org/10.1006/excr.2002.5658
  27. Njoo, M. D. and Westerhof, W., Vitiligo. Pathogenesis and treatment. Am. J. Clin. Dermatol., 2, 167-181 (2001) https://doi.org/10.2165/00128071-200102030-00006
  28. Park, K. C., Kim, D. S., Choi, H. O., Kim, K. H., Chung, J. H., Eun, H. C., Lee, J. S., and Seo, J. S., Overexpression of HSP70 prevents ultraviolet B-induced apoptosis of a human melanoma cell line. Arch. Dermatol. Res., 292, 482-487 (2000) https://doi.org/10.1007/s004030000173
  29. Park, K. H., Choi, H. O., Jang, D. D., Park, Y. I., and Park, K. C., Downregulation of Bcl-2 and activation of caspase-8 in the UVB-induced apoptosis of a cultured human melanoma cell line. Photodermatol. Photoimmunol. Photomed., 17, 218-222 (2001) https://doi.org/10.1034/j.1600-0781.2001.170503.x
  30. Pebay, A., Toutant, M., Premont, J., Calvo, C. F., Venance, L., Cordier, J., Glowinski, J., and Tence, M., Sphingosine-1-phosphate induces proliferation of astrocytes: regulation by intracellular signalling cascades. Eur. J. Neurosci., 13, 2067-2076 (2001) https://doi.org/10.1046/j.0953-816x.2001.01585.x
  31. Peus, D., Vasa, R. A., Beyerle, A., Meves, A., Krautmacher, C., and Pittelkow, M. R., UVB activates ERK1/2 and p38 signaling pathways via reactive oxygen species in cultured keratinocytes. J. Invest. Dermatol., 112, 751-756 (1999) https://doi.org/10.1046/j.1523-1747.1999.00584.x
  32. Pyne, S. and Pyne, N. J., Sphingosine 1-phosphate signalling in mammalian cells. Biochem. J., 349, 385-402 (2000) https://doi.org/10.1042/0264-6021:3490385
  33. Spiegel, S., Sphingosine 1-phosphate: a prototype of a new class of second messengers. J. Leukoc Biol., 65, 341-344 (1999) https://doi.org/10.1002/jlb.65.3.341
  34. Tada, A., Pereira, E., Beitner-Johnson, D., Kavanagh, R., and Abdel-Malek, Z. A., Mitogen- and ultraviolet-B-induced signaling pathways in normal human melanocytes. J. Invest. Dermatol., 118, 316-322 (2002) https://doi.org/10.1046/j.0022-202x.2001.01694.x
  35. Van Brocklyn, J. R., Graler, M. H., Bernhardt, G., Hobson, J. P., Lipp, M., and Spiegel, S., Sphingosine-1-phosphate is a ligand for the G protein-coupled receptor EDG-6. Blood., 95, 2624-2629 (2000)
  36. van Koppen, C. J., Meyer zu Heringdorf, D., Alemany, R., and Jakobs, K. H., Sphingosine kinase-mediated calcium signaling by muscarinic acetylcholine receptors. Life Sci., 68, 2535-2540 (2001) https://doi.org/10.1016/S0024-3205(01)01049-9
  37. Waetzig, V. and Herdegen, T., A single c-Jun N-terminal kinase isoform (JNK3-p54) is an effector in both neuronal differentiation and cell death. J. Biol. Chem. (2002)
  38. Watanabe, N., Iwamoto, T., Dickinson, D. A., Iles, K. E., and Forman, H. J., Activation of the mitochondrial caspase cascade in the absence of protein synthesis does not require c-Jun Nterminal kinase. Arch. Biochem. Biophys., 405, 231-240 (2002) https://doi.org/10.1016/S0003-9861(02)00399-5
  39. Xia, Z., Dickens, M., Raingeaud, J., Davis, R. J., and Greenberg, M. E., Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science, 270, 1326-1331 (1995) https://doi.org/10.1126/science.270.5240.1326
  40. Yanase, H., Ando, H., Horikawa, M., Watanabe, M., Mori, T., and Matsuda, N., Possible involvement of ERK 1/2 in UVAinduced melanogenesis in cultured normal human epidermal melanocytes. Pigment. Cell Res., 14, 103-109 (2001) https://doi.org/10.1034/j.1600-0749.2001.140205.x
  41. Zanke, B. W., Boudreau, K., Rubie, E., Winnett, E., Tibbles, L. A., Zon, L., Kyriakis, J., Liu, F. F., and Woodgett, J. R., The stress-activated protein kinase pathway mediates cell death following injury induced by cis-platinum, UV irradiation or heat. Curr. Biol., 6, 606-613 (1996) https://doi.org/10.1016/S0960-9822(02)00547-X
  42. Zhai, S., Yaar, M., Doyle, S. M., and Gilchrest, B. A., Nerve growth factor rescues pigment cells from ultraviolet-induced apoptosis by upregulating BCL-2 levels. Exp. Cell Res., 224, 335-343 (1996) https://doi.org/10.1006/excr.1996.0143
  43. Zhang, H., Shi, X., Zhang, Q. J., Hampong, M., Paddon, H., Wahyuningsih, D., and Pelech, S., Nocodazole-induced p53-dependent c-Jun N-terminal Kinase Activation Reduces Apoptosis in Human Colon Carcinoma HCT116 Cells. J. Biol. Chem., 277, 43648-43658 (2002) https://doi.org/10.1074/jbc.M203214200