{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T05:25:45Z","timestamp":1785216345678,"version":"3.55.0"},"reference-count":47,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2017,10,11]],"date-time":"2017-10-11T00:00:00Z","timestamp":1507680000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Korean Health Technology R&amp;D Project, Ministry of Health &amp; Welfare, Republic of Korea","award":["HN14C0086."],"award-info":[{"award-number":["HN14C0086."]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This study evaluated frequency-dependent effects of extremely low frequency electromagnetic fields (ELF-EMFs) on melanogenesis by melanocytes in vitro. Melanocytes were exposed to 2 mT EMFs at 30\u201375 Hz for 3 days before melanogenesis was examined. Exposure to ELF-EMFs at 50 and 60 Hz induced melanogenic maturation without cell damage, without changing cell proliferation and mitochondrial activity. Melanin content and tyrosinase activity of cells exposed to 50 Hz were higher than in controls, and mRNA expression of tyrosinase-related protein-2 was elevated relative to controls at 50 Hz. Phosphorylated cyclic adenosine monophosphate response element-binding protein (p-CREB) levels were higher than controls in cells exposed to ELF-EMFs at 50\u201375 Hz. Immunohistochemical staining showed that melanocyte-specific markers (HMB45, Melan-A) were strongly expressed in cells exposed to EMFs at 50 and 60 Hz compared to controls. Thus, exposure to ELF-EMFs at 50 Hz could stimulate melanogenesis in melanocytes, through activation of p-CREB and p-p38 and inhibition of phosphorylated extracellular signal-regulated protein kinase and phosphorylated stress-activated protein kinase\/c-Jun N-terminal kinase. The results may form the basis of an appropriate anti-gray hair treatment or be applied in a therapeutic device for inducing repigmentation in the skin of vitiligo patients.<\/jats:p>","DOI":"10.3390\/ijms18102120","type":"journal-article","created":{"date-parts":[[2017,10,11]],"date-time":"2017-10-11T12:17:47Z","timestamp":1507724267000},"page":"2120","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Effects of Extremely Low Frequency Electromagnetic Fields on Melanogenesis through p-ERK and p-SAPK\/JNK Pathways in Human Melanocytes"],"prefix":"10.3390","volume":"18","author":[{"given":"Yu-Mi","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Medical Biotechnology (BK21 Plus team), Dongguk University, Goyang-si 10326, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang-Eun","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology (BK21 Plus team), Dongguk University, Goyang-si 10326, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soo-Chan","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Electric and Electrical Engineering, Institute for Information Technology Convergence, Hankyong National University, Anseong-si 17579, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun-Joon","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology (BK21 Plus team), Dongguk University, Goyang-si 10326, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7533-9605","authenticated-orcid":false,"given":"Young-Kwon","family":"Seo","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology (BK21 Plus team), Dongguk University, Goyang-si 10326, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,10,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1590\/S0365-05962013000100009","article-title":"Mechanisms regulating melanogenesis","volume":"88","author":"Videira","year":"2013","journal-title":"Anais Bras Dermatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1111\/j.1751-1097.2007.00226.x","article-title":"The protective role of melanin against UV damage in human skin","volume":"84","author":"Brenner","year":"2008","journal-title":"Photochem. Photobiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1152\/physrev.2000.80.3.979","article-title":"Corticotropin Releasing Hormone and Proopiomelanocortin Involvement in the Cutaneous Response to Stress","volume":"80","author":"Slominski","year":"2000","journal-title":"Physiol. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1210\/er.2012-1092","article-title":"Key role of CRF in the skin stress response system","volume":"34","author":"Slominski","year":"2013","journal-title":"Endocr. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1152\/physrev.00044.2003","article-title":"Melanin Pigmentation in Mammalian Skin and Its Hormonal Regulation","volume":"84","author":"Slominski","year":"2004","journal-title":"Physiol. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1111\/j.1755-148X.2011.00898.x","article-title":"L-tyrosine and L-dihydroxyphenylalanine as hormone-like regulators of melanocyte functions","volume":"25","author":"Slominski","year":"2011","journal-title":"Pigment Cell Melanoma Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1111\/j.0022-202X.2004.23528.x","article-title":"Hair follicle pigmentation","volume":"124","author":"Slominski","year":"2005","journal-title":"J. Investig. Dermatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1111\/1346-8138.12570","article-title":"Prevention of hair graying by factors that promote the growth and differentiation of melanocytes","volume":"41","author":"Endou","year":"2014","journal-title":"J. Dermatol."},{"key":"ref_9","first-page":"981","article-title":"Genetic epidemiology of vitiligo: Multilocus recessivity cross-validated","volume":"55","author":"Nath","year":"1994","journal-title":"Am. J. Hum. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.sder.2009.04.008","article-title":"Vitiligo update","volume":"28","author":"Halder","year":"2009","journal-title":"Semin. Cutan. Med. Surg."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1111\/j.1600-0749.2007.00408.x","article-title":"Neurogenic dysregulation, oxidative stress, autoimmunity, and melanocytorrhagy in vitiligo: Can they be interconnected?","volume":"20","author":"Namazi","year":"2007","journal-title":"Pigment Cell Melanoma Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1610","DOI":"10.1111\/jdv.12619","article-title":"Narrowband ultraviolet B phototherapy in combination with other therapies for vitiligo: Mechanisms and efficacies","volume":"28","author":"Griffith","year":"2014","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_13","first-page":"41","article-title":"Low-level laser (light) therapy (LLLT) in skin: Stimulating, healing, restoring","volume":"32","author":"Avci","year":"2013","journal-title":"Semin. Cutan. Med. Surg."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1111\/j.1365-2133.2009.09152.x","article-title":"Low-energy helium-neon laser induces melanocyte proliferation via interaction with type IV collagen: Visible light as a therapeutic option for vitiligo","volume":"161","author":"Lan","year":"2009","journal-title":"Br. J. Dermatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1096\/fasebj.12.6.395","article-title":"Biological responses to electromagnetic fields","volume":"12","author":"Metcalfe","year":"1998","journal-title":"FASEB J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1002\/jor.20862","article-title":"Modulation of osteogenesis in human mesenchymal stem cells by specific pulsed electromagnetic field stimulation","volume":"27","author":"Tsai","year":"2009","journal-title":"J. Orthop. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1002\/bem.20550","article-title":"Pulsed electromagnetic fields accelerate proliferation and osteogenic gene expression in human bone marrow mesenchymal stem cells during osteogenic differentiation","volume":"31","author":"Sun","year":"2010","journal-title":"Bioelectromagnetics"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1007\/s007740200050","article-title":"The preventive effect on bone loss of 50-Hz, 1-mT electromagnetic field in ovariectomized rats","volume":"20","author":"Sert","year":"2002","journal-title":"J. Bone Mine Metab."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"920","DOI":"10.2106\/00004623-199274060-00014","article-title":"The effect of low-frequency electrical fields on osteogenesis","volume":"74","author":"McLeod","year":"1992","journal-title":"J. Bone Jt. Surg."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1002\/jcp.21293","article-title":"Extremely low frequency electromagnetic fields promote in vitro neurogenesis via upregulation of Ca(v)1-channel activity","volume":"215","author":"Piacentini","year":"2008","journal-title":"J. Cell Physiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.expneurol.2010.08.022","article-title":"Exposure to extremely low-frequency (50 Hz) electromagnetic fields enhances adult hippocampal neurogenesis in C57BL\/6 mice","volume":"226","author":"Cuccurazzu","year":"2010","journal-title":"Exp. Neurol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1002\/btpr.1607","article-title":"Neural stimulation on human bone marrow-derived mesenchymal stem cells by extremely low frequency electromagnetic fields","volume":"28","author":"Cho","year":"2012","journal-title":"Biotechnol. Prog."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1006\/jtbi.1993.1142","article-title":"melanocyte as \u201csensory\u201d and regulatory cells in the epidermis","volume":"164","author":"Slominski","year":"1993","journal-title":"J. Theor. Biol."},{"key":"ref_24","first-page":"113","article-title":"Evaluation of cyto\u00actoxicity in cultured cells by enzyme leakage","volume":"6","author":"Mitchell","year":"1980","journal-title":"Methods Cell Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1177\/026119290403200406","article-title":"Cellular effects of electromagnetic fields","volume":"32","author":"Naarala","year":"2004","journal-title":"Altern. Lab. Anim."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/2047-783X-19-37","article-title":"Low-frequency pulsed electromagnetic fields significantly improve time of closure and proliferation of human tendon fibroblasts","volume":"19","author":"Seeliger","year":"2014","journal-title":"Eur. J. Med. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"228","DOI":"10.3389\/fncel.2015.00228","article-title":"Impact of electromagnetic fields on stem cells: Common mechanisms at the crossroad between adult neurogenesis and osteogenesis","volume":"9","author":"Leone","year":"2015","journal-title":"Front. Cell Neurosci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.sjbs.2014.07.006","article-title":"Experimental model for ELF-EMF exposure: Concern for human health","volume":"22","author":"Costantini","year":"2015","journal-title":"Saudi J. Biol. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1096\/fj.00-0368com","article-title":"SCF\/c-kit signaling is required for cyclic regeneration of the hair pigmentation unit","volume":"15","author":"Botchkareva","year":"2001","journal-title":"FASEB J."},{"key":"ref_30","first-page":"613","article-title":"The tyrosinase gene family: Interactions of melanogenic proteins to regulate melanogenesis","volume":"40","author":"Winder","year":"1994","journal-title":"Cell. Mol. Biol. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1038\/34681","article-title":"MAP kinase links the transcription factor Microphthalmia to c-Kit signalling in melanocytes","volume":"391","author":"Hemesath","year":"1998","journal-title":"Nature"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1073\/pnas.92.5.1789","article-title":"Mitogenic and melanogenic stimulation of normal human melanocytes by melanotropic peptides","volume":"92","author":"Swope","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1242\/jcs.107.1.205","article-title":"Alpha-melanocyte stimulating hormone and its analogue Nle4DPhe7 alpha-MSH affect morphology, tyrosinase activity and melanogenesis in cultured human melanocytes","volume":"107","author":"Hunt","year":"1994","journal-title":"J. Cell Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1210\/endo.137.5.8612494","article-title":"Binding of melanotropic hormones to the melanocortin receptor MC1R on human melanocytes stimulates proliferation and melanogenesis","volume":"137","author":"Suzuki","year":"1996","journal-title":"Endocrinology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.jdermsci.2012.01.012","article-title":"The effects of NB-UVB on the hair follicle-derived neural crest stem cells differentiating into melanocyte lineage in vitro","volume":"66","author":"Dong","year":"2012","journal-title":"J. Dermatol. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1007\/s11010-011-0823-4","article-title":"Regulation of melanocyte pivotal transcription factor MITF by some other transcription factors","volume":"354","author":"Wan","year":"2011","journal-title":"Mol. Cell Biochem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1007\/s00403-011-1155-7","article-title":"Aromatic-turmerone inhibits \u03b1-MSH and IBMX-induced melanogenesis by inactivating CREB and MITF signaling pathways","volume":"303","author":"Park","year":"2011","journal-title":"Arch. Dermatol. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"892073","DOI":"10.1155\/2014\/892073","article-title":"Ginsenosides Rb1 and Rg1 Stimulate Melanogenesis in Human Epidermal Melanocytes via PKA\/CREB\/MITF Signaling","volume":"2014","author":"Lin","year":"2014","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"29","DOI":"10.4196\/kjpp.2015.19.1.29","article-title":"ERK Activation by Fucoidan Leads to Inhibition of Melanogenesis in Mel-Ab Cells","volume":"19","author":"Song","year":"2015","journal-title":"Korean J. Physiol. Pharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Kim, E.S., Jeon, H.B., Lim, H., Shin, J.H., Park, S.J., Jo, Y.K., Oh, W., Yang, Y.S., Cho, D.H., and Kim, J.Y. (2015). Conditioned Media from Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Inhibits Melanogenesis by Promoting Proteasomal Degradation of MITF. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0128078"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1007\/s00403-011-1158-4","article-title":"Ascorbic acid increases the activity and synthesis of tyrosinase in B16F10 cells through activation of p38 mitogen-activated protein kinase","volume":"303","author":"Lee","year":"2011","journal-title":"Arch. Dermatol. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1007\/s00403-009-1007-x","article-title":"A single UVB exposure increases the expression of functional KIT in human melanocytes by up-regulating MITF expression through the phosphorylation of p38\/CREB","volume":"302","author":"Mizutani","year":"2010","journal-title":"Arch. Dermatol. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/j.jep.2010.09.007","article-title":"Involvement of p38 MAPK signaling pathway in the anti-melanogenic effect of San-bai-tang, a Chinese herbal formula, in B16 cells","volume":"132","author":"Ye","year":"2010","journal-title":"J. Ethnopharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"842569","DOI":"10.1155\/2014\/842569","article-title":"[6]-Shogaol inhibits \u03b1-MSH-induced melanogenesis through the acceleration of ERK and PI3K\/Akt-mediated MITF degradation","volume":"2014","author":"Huang","year":"2014","journal-title":"BioMed Res. Int."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1111\/j.1600-0560.1989.tb00010.x","article-title":"HMB-45 recognizes stimulated melanocytes","volume":"16","author":"Smoller","year":"1989","journal-title":"J. Cutan. Pathol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1097\/00125480-199901000-00002","article-title":"Melan-A, a new melanocytic differentiation marker","volume":"6","author":"Busam","year":"1999","journal-title":"Adv. Anat. Pathol."},{"key":"ref_47","first-page":"209","article-title":"Mangosteen leaf extract increases melanogenesis in B16F1 melanoma cells by stimulating tyrosinase activity in vitro and by up-regulating tyrosinase gene expression","volume":"29","author":"Hamid","year":"2012","journal-title":"Int. J. Mol. Med."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/18\/10\/2120\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:46:58Z","timestamp":1760208418000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/18\/10\/2120"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,10,11]]},"references-count":47,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2017,10]]}},"alternative-id":["ijms18102120"],"URL":"https:\/\/doi.org\/10.3390\/ijms18102120","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,10,11]]}}}