Significance of the melanocortin 1 and endothelin B receptors in melanocyte homeostasis and prevention of sun-induced genotoxicity

Frontiers in Genetics

Volumn 7, Issue AUG, 2016, Pages

  Swope, Viki B ^a   Abdel Malek, Zalfa A ^a  

^a UNIVERSITY OF CINCINNATI COLLEGE OF MEDICINE   (United States)

Author keywords

DNA repair; Endothelin B receptor; Melanocortin 1 receptor; Melanocytes; Melanoma; Photoprotection; Ultraviolet radiation

Indexed keywords

8 HYDROXYDEOXYGUANOSINE; AFAMELANOTIDE; ALPHA INTERMEDIN; ATM PROTEIN; BETA DEFENSIN 3; CORTICOTROPIN; ENDOTHELIN 3; ENDOTHELIN B RECEPTOR; EUMELANIN; FIBROBLAST GROWTH FACTOR 2; FORSKOLIN; G PROTEIN COUPLED RECEPTOR; MELANOCORTIN 1 RECEPTOR; PHEOMELANIN; SCATTER FACTOR; STEM CELL FACTOR; SUNSCREEN; THEOPHYLLINE; XERODERMA PIGMENTOSUM GROUP A PROTEIN;

APOPTOSIS; CELL PROLIFERATION; DNA DAMAGE; DNA REPLICATION; EMBRYO DEVELOPMENT; GENETIC PREDISPOSITION; GENETIC VARIABILITY; GENOTOXICITY; HOMEOSTASIS; HUMAN; LOSS OF FUNCTION MUTATION; MELANOCYTE; MELANOGENESIS; MELANOMA SKIN CANCER; NONHUMAN; OXIDATIVE STRESS; PROTEIN PHOSPHORYLATION; REVIEW; SIGNAL TRANSDUCTION; SKIN PIGMENTATION; SUN EXPOSURE; ULTRAVIOLET RADIATION;

EID: 84988358347     PISSN: None     EISSN: 16648021     Source Type: Journal    
DOI: 10.3389/fgene.2016.00146     Document Type: Review

References (116)

1. Abbas, O., Miller, D. D., and Bhawan, J. (2014). Cutaneous malignant melanoma: update on diagnostic and prognostic biomarkers. Am. J. Dermatopathol. 36, 363-379. doi: 10.1097/DAD.0b013e31828a2ec5.
2. Abdel-Malek, Z., Swope, V., Suzuki, I., Im, S., Medrano, E. E., Nordlund, J., et al. (1995a). Paracrine regulation of human melanocytes by a-MSH, endothelin-1 basic FGF, and the agouti protein. Pigment Cell Res. Suppl. 4:24.
3. Abdel-Malek, Z., Swope, V. B., Pallas, J., Krug, K., and Nordlund, J. J. (1992). Mitogenic, melanogenic and cAMP responses of cultured neonatal human melanocytes to commonly used mitogens. J. Cell Physiol. 150, 416-425. doi: 10.1002/jcp.1041500226.
4. Abdel-Malek, Z., Swope, V. B., Suzuki, I., Akcali, C., Harriger, M. D., Boyce, S. T., et al. (1995b). Mitogenic and melanogenic stimulation of normal human melanocytes by melanotropic peptides. Proc. Natl. Acad. Sci. U.S.A. 92, 1789-1793. doi: 10.1073/pnas.92.5.1789.
5. Abdel-Malek, Z. A. (2010). Development of alpha-melanocortin analogs for melanoma prevention and targeting. Adv. Exp. Med. Biol. 681, 126-132. doi: 10.1007/978-1-4419-6354-3_10.
6. Abdel-Malek, Z. A., Kadekaro, A. L., Kavanagh, R. J., Todorovic, A., Koikov, L. N., McNulty, J. C., et al. (2006). Melanoma prevention strategy based on using tetrapeptide alpha-MSH analogs that protect human melanocytes from UV-induced DNA damage and cytotoxicity. FASEB J. 20, 1561-1563. doi: 10.1096/fj.05-5655fje.
7. Abdel-Malek, Z. A., Ruwe, A., Kavanagh-Starner, R., Kadekaro, A. L., Swope, V., Haskell-Luevano, C., et al. (2009). alpha-MSH tripeptide analogs activate the melanocortin 1 receptor and reduce UV-induced DNA damage in human melanocytes. Pigment Cell Melanoma Res. 22, 635-644. doi: 10.1111/j.1755-148X.2009.00598.x.
8. Adams, M. S., and Bronner-Fraser, M. (2009). Review: the role of neural crest cells in the endocrine system. Endocr. Pathol. 20, 92-100. doi: 10.1007/s12022-009-9070-6.
9. Alikhan, A., Felsten, L. M., Daly, M., and Petronic-Rosic, V. (2011). Vitiligo: a comprehensive overview Part I. Introduction, epidemiology, quality of life, diagnosis, differential diagnosis, associations, histopathology, etiology, and work-up. J. Am. Acad. Dermatol. 65, 473-491. doi: 10.1016/j.jaad.2010.11.061.
10. Barnetson, R. S., Ooi, T. K., Zhuang, L., Halliday, G. M., Reid, C. M., Walker, P. C., et al. (2006). [Nle4-D-Phe7]-alpha-melanocyte-stimulating hormone significantly increased pigmentation and decreased UV damage in fair-skinned Caucasian volunteers. J. Invest. Dermatol. 126, 1869-1878. doi: 10.1038/sj.jid.5700317.
11. Baynash, A. G., Hosoda, K., Giaid, A., Richardson, J. A., Emoto, N., Hammer, R. E., et al. (1994). Interaction of endothelin-3 with endothelin-B receptor is essential for development of epidermal melanocytes and enteric neurons. Cell 79, 1277-1285. doi: 10.1016/0092-8674(94)90018-3.
12. Beaumont, K. A., Newton, R. A., Smit, D. J., Leonard, J. H., Stow, J. L., and Sturm, R. A. (2005). Altered cell surface expression of human MC1R variant receptor alleles associated with red hair and skin cancer risk. Hum. Mol. Genet. 14, 2145-2154. doi: 10.1093/hmg/ddi219.
13. Bohm, M., Moellmann, G., Cheng, E., Alvarez-Franco, M., Wagner, S., Sassone-Corsi, P., et al. (1995). Identification of p90RSK as the probable CREB-Ser133 kinase in human melanocytes. Cell Growth Differ. 6, 291-302.
14. Bohm, M., Wolff, I., Scholzen, T. E., Robinson, S. J., Healy, E., Luger, T. A., et al. (2005). alpha-melanocyte-stimulating hormone protects from ultraviolet radiation-induced apoptosis and DNA damage. J. Biol. Chem. 280, 5795-5802. doi: 10.1074/jbc.M406334200.
15. Box, N. F., Duffy, D. L., Chen, W., Stark, M., Martin, N. G., Sturm, R. A., et al. (2001). MC1R genotype modifies risk of melanoma in families segregating CDKN2A mutations. Am. J. Hum. Genet. 69, 765-773. doi: 10.1086/323412.
16. Box, N. F., Wyeth, J. R., O'Gorman, L. E., Martin, N. G., and Sturm, R. A. (1997). Characterization of melanocyte stimulating hormone receptor variant alleles in twins with red hair. Hum. Mol. Genet. 6, 1891-1897. doi: 10.1093/hmg/6.11.1891.
17. Budden, T., and Bowden, N. A. (2013). The role of altered nucleotide excision repair and UVB-induced DNA damage in melanomagenesis. Int. J. Mol. Sci. 14, 1132-1151. doi: 10.3390/ijms14011132.
18. Bustamante, J., Bredeston, L., Malanga, G., and Mordoh, J. (1993). Role of melanin as a scavenger of active oxygen species. Pigment Cell Res. 6, 348-353. doi: 10.1111/j.1600-0749.1993.tb00612.x.
19. Candille, S. I., Kaelin, C. B., Cattanach, B. M., Yu, B., Thompson, D. A., Nix, M. A., et al. (2007). A-defensin mutation causes black coat color in domestic dogs. Science 318, 1418-1423. doi: 10.1126/science.1147880.
20. Castrucci, A. M. L., Hadley, M. E., Sawyer, T. K., Wilkes, B. C., Al-Obeidi, F., Staples, D. J., et al. (1989). Alpha-Melanotropin: the minimal active sequence in the lizard skin bioassay. Gen. Comp. Endocrinol. 73, 157-163. doi: 10.1016/0016-6480(89)90066-X.
21. Celeste, A., Petersen, S., Romanienko, P. J., Fernandez-Capetillo, O., Chen, H. T., Sedelnikova, O. A., et al. (2002). Genomic instability in mice lacking histone H2AX. Science 296, 922-927. doi: 10.1126/science.1069398.
22. Cimprich, K. A., and Cortez, D. (2008). ATR: an essential regulator of genome integrity. Nat. Rev. Mol. Cell Biol. 9, 616-627. doi: 10.1038/nrm2450.
23. Denat, L., Kadekaro, A. L., Marrot, L., Leachman, S. A., and Abdel-Malek, Z. A. (2014). Melanocytes as instigators and victims of oxidative stress. J. Invest. Dermatol. 134, 1512-1518. doi: 10.1038/jid.2014.65.
24. DiGiovanna, J. J., and Kraemer, K. H. (2012). Shining a light on xeroderma pigmentosum. J. Invest. Dermatol. 132(3 Pt 2), 785-796. doi: 10.1038/jid.2011.426.
25. Dubin, N., Moseson, M., and Pasternack, B. S. (1989). Sun exposure and malignant melanoma among susceptible individuals. Environ. Health Perspect. 81, 139-151. doi: 10.1289/ehp.8981139.
26. Eisinger, M., and Marko, O. (1982). 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. doi: 10.1073/pnas.79.6.2018.
27. Garcia-Borron, J. C., Abdel-Malek, Z., and Jimenez-Cervantes, C. (2014). MC1R, the cAMP pathway, and the response to solar UV: extending the horizon beyond pigmentation. Pigment Cell Melanoma Res. 27, 699-720. doi: 10.1111/pcmr.12257.
28. Geschwind, I. I., Huseby, R. A., and Nishioka, R. (1972). The effect of melanocyte-stimulating hormone on coat color in the mouse. Recent Prog. Horm. Res. 28, 91-130.
29. Gilchrest, B. A., Eller, M. S., Geller, A. C., and Yaar, M. (1999). The pathogenesis of melanoma induced by ultraviolet radiation. New Engl. J. Med. 340, 1341-1348. doi: 10.1056/NEJM199904293401707.
30. Gomez-Lazaro, M., Fernandez-Gomez, F. J., and Jordan, J. (2004). p53: twenty five years understanding the mechanism of genome protection. J. Physiol. Biochem. 60, 287-307. doi: 10.1007/BF03167075.
31. Grichnik, J. M., Burch, J. A., Burchette, J., and Shea, C. R. (1998). The SCF/KIT pathway plays a critical role in the control of normal human melanocyte homeostasis. J. Invest. Dermatol. 111, 233-238. doi: 10.1046/j.1523-1747.1998.00272.x.
32. Halaban, R., Langdon, R., Birchall, N., Cuono, C., Baird, A., Scott, G., et al. (1988a). Basic fibroblast growth factor from human keratinocytes is a natural mitogen for melanocytes. J. Cell Biol. 107, 1611-1619. doi: 10.1083/jcb.107.4.1611.
33. Halaban, R., Langdon, R., Birchall, N., Cuono, C., Baird, A., Scott, G., et al. (1988b). Paracrine stimulation of melanocytes by keratinocytes through basic fibroblast growth factor. Annals N. Y. Acad. Sci. 548, 180-190. doi: 10.1111/j.1749-6632.1988.tb18805.x.
34. Halder, R. M., and Bridgeman-Shah, S. (1995). Skin cancer in African Americans. Cancer 75, 667-673.
35. Han, J., Kraft, P., Colditz, G. A., Wong, J., and Hunter, D. J. (2006). Melanocortin 1 receptor variants and skin cancer risk. Int. J. Cancer 119, 1976-1984.
36. Hanawalt, P. C. (2002). Subpathways of nucleotide excision repair and their regulation. Oncogene 21, 8949-8956. doi: 10.1038/sj.onc.1206096.
37. Harding, R. M., Healy, E., Ray, A. J., Ellis, N. S., Flanagan, N., Todd, C., et al. (2000). Evidence for variable selective pressures at MC1R. Am. J. Hum. Genet. 66, 1351-1361. doi: 10.1086/302863.
38. Hauser, J. E., Kadekaro, A. L., Kavanagh, R. J., Wakamatsu, K., Terzieva, S., Schwemberger, S., et al. (2006). Melanin content and MC1R function independently affect UVR-induced DNA damage in cultured human melanocytes. Pigment Cell Res. 19, 303-314. doi: 10.1111/j.1600-0749.2006.00315.x.
39. Hennessy, A., Oh, C., Diffey, B., Wakamatsu, K., Ito, S., and Rees, J. (2005). Eumelanin and pheomelanin concentrations in human epidermis before and after UVB irradiation. Pigment Cell Res. 18, 220-223. doi: 10.1111/j.1600-0749.2005.00233.x.
40. Hirobe, T., and Takeuchi, T. (1977). Induction of melanogenesis in vitro in the epidermal melanoblasts of newborn mouse skin by MSH. In Vitro 13, 311-315. doi: 10.1007/BF02616177.
41. Hruby, V. J., Wilkes, B. C., Hadley, M. D., Al-Obeidi, F., Sawyer, T. K., Staples, D. J., et al. (1987). a-Melanotropin: the minimal active sequence in the frog skin bioassay. J. Med. Chem. 30, 2126-2130. doi: 10.1021/jm00394a033.
42. Hunt, G., Kyne, S., Ito, S., Wakamatsu, K., Todd, C., and Thody, A. (1995a). Eumelanin and phaeomelanin contents of human epidermis and cultured melanocytes. Pigment Cell Res. 8, 202-208. doi: 10.1111/j.1600-0749.1995.tb00664.x.
43. Hunt, G., Kyne, S., Wakamatsu, K., Ito, S., and Thody, A. J. (1995b). Nle4DPhe7 alpha-melanocyte-stimulating hormone increases the eumelanin:phaeomelanin ratio in cultured human melanocytes. J. Invest. Dermatol. 104, 83-85. doi: 10.1111/1523-1747.ep12613565.
44. Hyter, S., Coleman, D. J., Ganguli-Indra, G., Merrill, G. F., Ma, S., Yanagisawa, M., et al. (2013). Endothelin-1 is a transcriptional target of p53 in epidermal keratinocytes and regulates ultraviolet-induced melanocyte homeostasis. Pigment Cell Melanoma Res. 26, 247-258. doi: 10.1111/pcmr.12063.
45. Im, S., Moro, O., Peng, F., Medrano, E. E., Cornelius, J., Babcock, G., et al. (1998). Activation of the cyclic AMP pathway by alpha-melanotropin mediates the response of human melanocytes to ultraviolet B radiation. Cancer Res. 58, 47-54.
46. Imokawa, G., Kobayashi, T., Miyagishi, M., Higashi, K., and Yada, Y. (1997). The role of endothelin-1 in epidermal hyperpigmentation and signaling mechanisms of mitogenesis and melanogenesis. Pigment Cell Res. 10, 218-228. doi: 10.1111/j.1600-0749.1997.tb00488.x.
47. Imokawa, G., Miyagishi, M., and Yada, Y. (1995). Endothelin-1 as a new melanogen: coordinated expression of its gene and the tyrosinase gene in UVB-exposed human epidermis. J. Invest. Dermatol. 105, 32-37. doi: 10.1111/1523-1747.ep12312500.
48. Imokawa, G., Yada, Y., and Miyagishi, M. (1992). Endothelins secreted from human keratinocytes are intrinsic mitogens for human melanocytes. J. Biol. Chem. 267, 24675-24680.
49. Jarrett, S. G., Horrell, E. M., Christian, P. A., Vanover, J. C., Boulanger, M. C., Zou, Y., et al. (2014). PKA-mediated phosphorylation of ATR promotes recruitment of XPA to UV-induced DNA damage. Mol. Cell 54, 999-1011. doi: 10.1016/j.molcel.2014.05.030.
50. Kadekaro, A. L., Chen, J., Yang, J., Chen, S., Jameson, J., Swope, V. B., et al. (2012). Alpha-melanocyte-stimulating hormone suppresses oxidative stress through a p53-mediated signaling pathway in human melanocytes. Mol. Cancer Res. 10, 778-786. doi: 10.1158/1541-7786.MCR-11-0436.
51. Kadekaro, A. L., Kavanagh, R., Kanto, H., Terzieva, S., Hauser, J., Kobayashi, N., et al. (2005). alpha-Melanocortin and endothelin-1 activate antiapoptotic pathways and reduce DNA damage in human melanocytes. Cancer Res. 65, 4292-4299. doi: 10.1158/0008-5472.CAN-04-4535.
52. Kadekaro, A. L., Kavanagh, R. J., Wakamatsu, K., Ito, S., Pipitone, M. A., and Abdel-Malek, Z. A. (2003). Cutaneous photobiology. The melanocyte vs. the sun: who will win the final round? Pigment Cell Res. 16, 434-447. doi: 10.1034/j.1600-0749.2003.00088.x.
53. Kadekaro, A. L., Leachman, S., Kavanagh, R. J., Swope, V., Cassidy, P., Supp, D., et al. (2010). Melanocortin 1 receptor genotype: an important determinant of the damage response of melanocytes to ultraviolet radiation. FASEB J. 24, 3850-3860. doi: 10.1096/fj.10-158485.
54. Kakurai, M., Fujita, N., Kiyosawa, T., Inoue, T., Ishibashi, S., Furukawa, Y., et al. (2002). Vasoactive intestinal peptide and cytokines enhance stem cell factor production from epidermal keratinocytes DJM-1. J. Invest. Dermatol. 119, 1183-1188. doi: 10.1046/j.1523-1747.2002.19506.x.
55. Kanetsky, P. A., Panossian, S., Elder, D. E., Guerry, D., Ming, M. E., Schuchter, L., et al. (2010). Does MC1R genotype convey information about melanoma risk beyond risk phenotypes? Cancer 116, 2416-2428. doi: 10.1002/cncr.24994.
56. Kanetsky, P. A., Rebbeck, T. R., Hummer, A. J., Panossian, S., Armstrong, B. K., Kricker, A., et al. (2006). Population-based study of natural variation in the melanocortin-1 receptor gene and melanoma. Cancer Res. 66, 9330-9337. doi: 10.1158/0008-5472.CAN-06-1634.
57. Kennedy, C., ter Huurne, J., Berkhout, M., Gruis, N., Bastiaens, M., Bergman, W., et al. (2001). Melanocortin 1 receptor (MC1R) gene variants are associated with an increased risk for cutaneous melanoma which is largely independent of skin type and hair color. J. Invest. Dermatol. 117, 294-300. doi: 10.1046/j.0022-202x.2001.01421.x.
58. Kokot, A., Metze, D., Mouchet, N., Galibert, M. D., Schiller, M., Luger, T. A., et al. (2009). Alpha-melanocyte-stimulating hormone counteracts the suppressive effect of UVB on Nrf2 and Nrf-dependent gene expression in human skin. Endocrinology 150, 3197-3206. doi: 10.1210/en.2008-1315.
59. Kondo, T., and Hearing, V. J. (2011). Update on the regulation of mammalian melanocyte function and skin pigmentation. Exp. Rev. Dermatol. 6, 97-108. doi: 10.1586/edm.10.70.
60. Kraemer, K. H., Lee, M.-M., Andrews, A. D., and Lambert, W. C. (1994). The role of sunlight and DNA repair in melanoma and nonmelanoma skin cancer. The xeroderma pigmentosum paradigm. Arch. Dermatol. 130, 1018-1021. doi: 10.1001/archderm.1994.01690080084012.
61. Kreider, J. W., Rosenthal, M., and Lengle, N. (1973). Cyclic adenosine 3,5-monophosphate in the control of melanoma cell replication and differentiation. J. Natl Cancer Inst. 50, 555-558.
62. Kunisada, T., Yoshida, H., Yamazaki, H., Miyamoto, A., Hemmi, H., Nishimura, E., et al. (1998). Transgene expression of steel factor in the basal layer of epidermis promotes survival, proliferation, differentiation and migration of melanocyte precursors. Development 125, 2915-2923.
63. Landi, M. T., Kanetsky, P. A., Tsang, S., Gold, B., Munroe, D., Rebbeck, T., et al. (2005). MC1R, ASIP, and DNA repair in sporadic and familial melanoma in a Mediterranean population. J. Natl. Cancer Inst. 97, 998-1007. doi: 10.1093/jnci/dji176.
64. Lee, H. O., Levorse, J. M., and Shin, M. K. (2003). The endothelin receptor-B is required for the migration of neural crest-derived melanocyte and enteric neuron precursors. Dev. Biol. 259, 162-175. doi: 10.1016/S0012-1606(03)00160-X.
65. Legros, F., Coel, J., Doyen, A., Hanson, P., Van-Tieghem, N., Vercammen-Grandjean, A., et al. (1981). Alpha-melanocyte-stimulating hormone binding and biological activity in a human melanoma cell line. Cancer Res. 41, 1539-1544.
66. Lerner, A. B., and McGuire, J. S. (1961). Effect of alpha-and beta-melanocyte stimulating hormones on the skin colour of man. Nature 189, 176-179. doi: 10.1038/189176a0.
67. Levine, N., Sheftel, S. N., Eytan, T., Dorr, R. T., Hadley, M. E., Weinrach, J. C., et al. (1991). Induction of skin tanning by the subcutaneous administration of a potent synthetic melanotropin. JAMA 266, 2730-2736. doi: 10.1001/jama.266.19.2730.
68. Marwan, M. M., Abdel Malek, Z. A., Kreutzfeld, K. L., Hadley, M. E., Wilkes, B. C., Hruby, V. J., et al. (1985). Stimulation of S91 melanoma tyrosinase activity by superpotent alpha-melanotropins. Mol. Cell Endocrinol. 41, 171-177. doi: 10.1016/0303-7207(85)90020-6.
69. Matsumoto, K., Tajima, H., and Nakamura, T. (1991). Hepatocyte growth factor is a potent stimulator of human melanocyte DNA synthesis and growth. Biochem. Biophys. Res. Commun. 176, 45-51. doi: 10.1016/0006-291X(91)90887-D.
70. Menon, A., Persad, A., Ranadine, N. S., and Haberman, H. F. (1983). Effects of ultraviolet-visible radiation in the presence of melanin isolated from human black or red hair upon Ehrlich ascites carcinoma cells. Cancer Res. 43, 3165-3169.
71. Meredith, P., and Sarna, T. (2006). The physical and chemical properties of eumelanin. Pigment Cell Res. 19, 572-594. doi: 10.1111/j.1600-0749.2006.00345.x.
72. Mildner, M., Mlitz, V., Gruber, F., Wojta, J., and Tschachler, E. (2007). Hepatocyte growth factor establishes autocrine and paracrine feedback loops for the protection of skin cells after UV irradiation. J. Invest. Dermatol. 127, 2637-2644. doi: 10.1038/sj.jid.5700938.
73. Mitra, D., Luo, X., Morgan, A., Wang, J., Hoang, M. P., Lo, J., et al. (2012). An ultraviolet-radiation-independent pathway to melanoma carcinogenesis in the red hair/fair skin background. Nature 491, 449-453. doi: 10.1038/nature11624.
74. Mizuno, N., Kokubu, H., Sato, M., Nishimura, A., Yamauchi, J., Kurose, H., et al. (2005). G protein-coupled receptor signaling through Gq and JNK negatively regulates neural progenitor cell migration. Proc. Natl. Acad. Sci. U.S.A. 102, 12365-12370. doi: 10.1073/pnas.0506101102.
75. Mountjoy, K. G., Robbins, L. S., Mortrud, M. T., and Cone, R. D. (1992). The cloning of a family of genes that encode the melanocortin receptors. Science 257, 1248-1251. doi: 10.1126/science.1325670.
76. Nofsinger, J. B., Liu, Y., and Simon, J. D. (2002). Aggregation of eumelanin mitigates photogeneration of reactive oxygen species. Free Radic. Biol. Med. 32, 720-730. doi: 10.1016/S0891-5849(02)00763-3.
77. Palmer, J. S., Duffy, D. L., Box, N. F., Aitken, J. F., O'Gorman, L. E., Green, A. C., et al. (2000). Melanocortin-1 receptor polymorphisms and risk of melanoma: is the association explained solely by pigmentation phenotype? Am. J. Hum. Genet. 66, 176-186. doi: 10.1086/302711.
78. Panzella, L., Leone, L., Greco, G., Vitiello, G., D'Errico, G., Napolitano, A., et al. (2014). Red human hair pheomelanin is a potent pro-oxidant mediating UV-independent contributory mechanisms of melanomagenesis. Pigment Cell Melanoma Res. 27, 244-252. doi: 10.1111/pcmr.12199.
79. Pasquali, E., Garcia-Borron, J. C., Fargnoli, M. C., Gandini, S., Maisonneuve, P., Bagnardi, V., et al. (2015). MC1R variants increased the risk of sporadic cutaneous melanoma in darker-pigmented Caucasians: a pooled-analysis from the M-SKIP project. Int. J. Cancer 136, 618-631. doi: 10.1002/ijc.29018.
80. Pathak, M. A. (1995). "Functions of melanin and protection by melanin," in Melanin: Its Role in Human Photoprotection, eds L. Zeise, M. R. Chedekel, and T. B. Fitzpatrick (Overland Park: Valdenmar Publishing Company).
81. Pathak, M. A., Hori, Y., Szabo, G., and Fitzpatrick, T. B. (1971). "The photobiology of melanin pigmentation in human skin," in Biology of Normal and Abnormal Melanocytes, eds T. Kawamura, T. B. Fitzpatrick, and M. Seiji (Baltimore: University Park Press).
82. Pathak, M. A., Jimbow, K., and Fitzpatrick, T. (1980). "Photobiology of pigment cell," in Phenotypic Expression in Pigment Cells, ed. M. Seiji (Tokyo: University of Tokyo Press).
83. Pawelek, J., Wong, G., Sansone, M., and Morowitz, J. (1973). Molecular biology of pigment cells: molecular controls in mammalian pigmentation. Yale J. Biol. Med. 46, 430-443.
84. Premi, S., Wallisch, S., Mano, C. M., Weiner, A. B., Bacchiocchi, A., Wakamatsu, K., et al. (2015). Photochemistry. Chemiexcitation of melanin derivatives induces DNA photoproducts long after UV exposure. Science 347, 842-847. doi: 10.1126/science.1256022.
85. Ringholm, A., Klovins, J., Rudzish, R., Phillips, S., Rees, J. L., and Schioth, H. B. (2004). Pharmacological characterization of loss of function mutations of the human melanocortin 1 receptor that are associated with red hair. J. Invest. Dermatol. 123, 917-923. doi: 10.1111/j.0022-202X.2004.23444.x.
86. Robbins, L. S., Nadeau, J. H., Johnson, K. R., Kelly, M. A., Roselli-Rehfuss, L., Baack, E., et al. (1993). Pigmentation phenotypes of variant extension locus alleles result from point mutations that alter MSH receptor function. Cell 72, 827-834. doi: 10.1016/0092-8674(93)90572-8.
87. Rubanyi, G. M., and Polokoff, M. A. (1994). Endothelins: molecular biology, biochemistry, pharmacology, physiology, and pathophysiology. Pharmacol. Rev. 46, 325-415.
88. Sanchez Mas, J., Olivares Sanchez, C., Ghanem, G., Haycock, J., Lozano Teruel, J. A., Garcia-Borron, J. C., et al. (2002). Loss-of-function variants of the human melanocortin-1 receptor gene in melanoma cells define structural determinants of receptor function. Eur. J. Biochem. 269, 6133-6141. doi: 10.1046/j.1432-1033.2002.03329.x.
89. Sanchez-Laorden, B. L., Herraiz, C., Valencia, J. C., Hearing, V. J., Jimenez-Cervantes, C., and Garcia-Borron, J. C. (2009). Aberrant trafficking of human melanocortin 1 receptor variants associated with red hair and skin cancer: steady-state retention of mutant forms in the proximal golgi. J. Cell Physiol. 220, 640-654. doi: 10.1002/jcp.21804.
90. Sawyer, T. K., Hruby, V. J., Wilkes, B. C., Draelos, M. T., Hadley, M. E., and Bergsneider, M. (1982). Comparative biological activities of highly potent active-site analogues of a-melanotropin. J. Med. Chem. 25, 1022-1027. doi: 10.1021/jm00351a004.
91. Sawyer, T. K., Sanfilippo, P. J., Hruby, V. J., Engel, M. H., Heward, C. B., Burnett, J. B., et al. (1980). 4-Norleucine, 7-D-phenylalanine-a-melanocyte-stimulating hormone: a highly potent a-melanotropin with ultralong biological activity. Proc. Natl. Acad. Sci. U.S.A. 77, 5754-5758. doi: 10.1073/pnas.77.10.5754.
92. Schaffer, J. V., and Bolognia, J. L. (2001). The melanocortin-1 receptor: red hair and beyond. Arch. Dermatol. 137, 1477-1485. doi: 10.1001/archderm.137.11.1477.
93. Schauer, E., Trautinger, F., Kock, A., Schwarz, A., Bhardwaj, R., Simon, M., et al. (1994). Proopiomelanocortin-derived peptides are synthesized and released by human keratinocytes. J. Clin. Invest. 93, 2258-2262. doi: 10.1172/JCI117224.
94. Scott, G., Cassidy, L., and Abdel-Malek, Z. (1997). a-Melanocyte-stimulating hormone and endothelin-1 have opposing effects on melanocyte adhesion, migration, and pp125FAK phosphorylation. Exp. Cell Res. 237, 19-28. doi: 10.1006/excr.1997.3765.
95. Scott, M. C., Wakamatsu, K., Ito, S., Kadekaro, A. L., Kobayashi, N., Groden, J., et al. (2002). Human melanocortin 1 receptor variants, receptor function and melanocyte response to UV radiation. J. Cell Sci. 115(Pt 11), 2349-2355.
96. Silvers, W. K. (1961). Genes and the pigment cells of mammals. Science 134, 368-373. doi: 10.1126/science.134.3476.368.
97. Smith, A. G., Luk, N., Newton, R. A., Roberts, D. W., Sturm, R. A., and Muscat, G. E. (2008). Melanocortin-1 receptor signaling markedly induces the expression of the NR4A nuclear receptor subgroup in melanocytic cells. J. Biol. Chem. 283, 12564-12570. doi: 10.1074/jbc.M800480200.
98. Smith, R., Healy, E., Siddiqui, S., Flanagan, N., Steijlen, P. M., Rosdahl, I., et al. (1998). Melanocortin 1 receptor variants in Irish population. J. Invest. Dermatol. 111, 119-122. doi: 10.1046/j.1523-1747.1998.00252.x.
99. Song, X., Mosby, N., Yang, J., Xu, A., Abdel-Malek, Z., and Kadekaro, A. L. (2009). alpha-MSH activates immediate defense responses to UV-induced oxidative stress in human melanocytes. Pigment Cell Melanoma Res. 22, 809-818. doi: 10.1111/j.1755-148X.2009.00615.x.
100. Stratigos, A. J., Dimisianos, G., Nikolaou, V., Poulou, M., Sypsa, V., Stefanaki, I., et al. (2006). Melanocortin receptor-1 gene polymorphisms and the risk of cutaneous melanoma in a low-risk southern European population. J. Invest. Dermatol. 126, 1842-1849. doi: 10.1038/sj.jid.5700292.
101. Suzuki, I., Cone, R. D., Im, S., Nordlund, J., and Abdel-Malek, Z. A. (1996). Binding of melanotropic hormones to the melanocortin receptor MC1R on human melanocytes stimulates proliferation and melanogenesis. Endocrinology 137, 1627-1633. doi: 10.1210/en.137.5.1627.
102. Suzuki, I., Tada, A., Ollmann, M. M., Barsh, G. S., Im, S., Lamoreux, M. L., et al. (1997). Agouti signaling protein inhibits melanogenesis and the response of human melanocytes to alpha-melanotropin. J. Invest. Dermatol. 108, 838-842. doi: 10.1111/1523-1747.ep12292572.
103. Swope, V., Alexander, C., Starner, R., Schwemberger, S., Babcock, G., and Abdel-Malek, Z. A. (2014). Significance of the melanocortin 1 receptor in the DNA damage response of human melanocytes to ultraviolet radiation. Pigment Cell Melanoma Res. 27, 601-610. doi: 10.1111/pcmr.12252.
104. Swope, V. B., Jameson, J. A., McFarland, K. L., Supp, D. M., Miller, W. E., McGraw, D. W., et al. (2012). Defining MC1R regulation in human melanocytes by its agonist alpha-Melanocortin and Antagonists Agouti Signaling Protein and beta-Defensin 3. J. Invest. Dermatol. 132, 2255-2262. doi: 10.1038/jid.2012.135.
105. Swope, V. B., Medrano, E. E., Smalara, D., and Abdel-Malek, Z. A. (1995). Long-term proliferation of human melanocytes is supported by the physiologic mitogens alpha-melanotropin, endothelin-1, and basic fibroblast growth factor. Exp. Cell Res. 217, 453-459. doi: 10.1006/excr.1995.1109.
106. Tada, A., Pereira, E., Beitner-Johnson, D., Kavanagh, R., and Abdel-Malek, Z. A. (2002). Mitogen-and ultraviolet-B-induced signaling pathways in normal human melanocytes. J. Invest. Dermatol. 118, 316-322. doi: 10.1046/j.0022-202x.2001.01694.x.
107. Tada, A., Suzuki, I., Im, S., Davis, M. B., Cornelius, J., Babcock, G., et al. (1998). Endothelin-1 is a paracrine growth factor that modulates melanogenesis of human melanocytes and participates in their responses to ultraviolet radiation. Cell Growth Differ. 9, 575-584.
108. Tadokoro, T., Kobayashi, N., Zmudzka, B. Z., Ito, S., Wakamatsu, K., Yamaguchi, Y., et al. (2003). UV-induced DNA damage and melanin content in human skin differing in racial/ethnic origin. FASEB J. 17, 1177-1179.
109. Tamate, H. B., and Takeuchi, T. (1984). Action of the e locus of mice in the response of phaeomelanic hair follicles to a-melanocyte-stimulating hormone in vitro. Science 224, 1241-1242. doi: 10.1126/science.6328651.
110. Tamura, A., Halaban, R., Moellmann, G., Cowan, J. M., Lerner, M. R., and Lerner, A. B. (1987). Normal murine melanocytes in culture. In Vitro Cell. Dev. Biol. 23, 519-522. doi: 10.1007/BF02628423.
111. van der Velden, P. A., Sandkuijl, L. A., Bergman, W., Pavel, S., van Mourik, L., Frants, R. R., et al. (2001). Melanocortin-1 receptor variant R151C modifies melanoma risk in Dutch families with melanoma. Am. J. Hum. Genet. 69, 774-779. doi: 10.1086/323411.
112. von Koschembahr, A. M., Swope, V. B., Starner, R. J., and Abdel-Malek, Z. A. (2015). Endothelin-1 protects human melanocytes from UV-Induced DNA damage by activating JNK and p38 signaling pathways. Exp. Dermatol. 24, 269-274. doi: 10.1111/exd.12638.
113. Wade, D. R., and Burkart, M. E. (1978). The role of adenosine 3,5-cyclic monophosphate in the density-dependent regulation of growth and tyrosinase activity of B-16 melanoma cells. J. Cell Physiol. 94, 265-273. doi: 10.1002/jcp.1040940304.
114. Wakamatsu, K., Graham, A., Cook, D., and Thody, A. J. (1997). Characterization of ACTH peptides in human skin and their activation of the melanocortin-1 receptor. Pigment Cell Res. 10, 288-297. doi: 10.1111/j.1600-0749.1997.tb00688.x.
115. Wakamatsu, K., Kavanagh, R., Kadekaro, A. L., Terzieva, S., Strum, R. A., Leachman, S., et al. (2006). Diversity of pigmentation in cultured human melanocytes is due to differences in the type as well as quantity of melanin. Pigment Cell Res. 19, 154-162. doi: 10.1111/j.1600-0749.2006.00293.x.
116. Yada, Y., Higuchi, K., and Imokawa, G. (1991). Effects of endothelins on signal transduction and proliferation in human melanocytes. J. Biol. Chem. 266, 18352-18357.