title: Melanin production through novel processing of proopiomelanocortin in the extracellular compartment of the auricular skin of C57BL/6 mice after UV-irradiation.
abstract: The production of melanin is regulated by α-melanocyte-stimulating hormone (α-MSH), which is produced from proopiomelanocortin (POMC). Keratinocytes release POMC along with lower levels of α-MSH and ACTH. To clarify the mechanism of melanogenesis after ultraviolet (UV)-irradiation, this study focused on the expression of POMC and POMC-derived peptides after UV-irradiation. Western blot analysis and immunoassays indicated that both POMC and α-MSH-like immunoreactivity (α-MSH-LI) increased after UV-irradiation. However, other POMC-derived products were very low. In hypophysectomized mice, α-MSH-LI increased to the same level as in control mice after UV-irradiation. Structural analysis revealed that the major α-MSH-LI product was ACTH(1-8). Furthermore, ACTH(1-8) competed with [(125)I]-α-MSH for receptor binding and increased melanin production via a melanocortin-1 receptor. These results suggested that melanin was produced through ACTH(1-8) after UV-irradiation. Trypsin-like enzymatic activity, which is responsible for POMC activation, increased after UV-irradiation and was identified as tryptase. In mast cell-deficient mice, which do not produce tryptase, α-MSH-LI levels were unchanged after UV-irradiation. The present study demonstrates the production of ACTH(1-8) from POMC by tryptase, which is a novel peptide-processing mechanism in the extracellular compartment of the skin.
authors.affiliation: Department of Microbiology and Molecular Cell Biology, Nihon Pharmaceutical University, 10281 Komuro, Ina-machi, Kitaadachi-gun, Saitama, 362-0806, Japan.|Laboratory of Bioorganic Chemistry School of Pharmaceutical Sciences University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamamoto
authors.affiliation: Laboratory of Bioorganic Chemistry School of Pharmaceutical Sciences University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Yamane
authors.affiliation: Laboratory of Bioorganic Chemistry School of Pharmaceutical Sciences University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Iguchi
authors.affiliation: Department of Research and Development, Ichimaru Pharcos Co. Ltd, 318-1 Asagi, Motosu City, Gifu 501-0475, Japan.
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Department of Research and Development, Ichimaru Pharcos Co. Ltd, 318-1 Asagi, Motosu City, Gifu 501-0475, Japan.
authors.forename: Arunasiri
authors.initials: A
authors.lastname: Iddamalgoda
authors.affiliation: Laboratory of Bioorganic Chemistry School of Pharmaceutical Sciences University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Unno
authors.affiliation: Laboratory of Bioorganic Chemistry School of Pharmaceutical Sciences University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Hoshino
authors.affiliation: Laboratory of Bioorganic Chemistry School of Pharmaceutical Sciences University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takeda
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D054644:Ear Auricle; D005110:Extracellular Space / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism; D008543:Melanins / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000378:metabolism*; D011485:Protein Binding; D044102:Receptor, Melanocortin, Type 1 / Q000378:metabolism; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000378:metabolism* / Q000528:radiation effects*; D014466:Ultraviolet Rays; D000521:alpha-MSH / Q000276:immunology / Q000378:metabolism
chemical_list: D008543:Melanins; D010455:Peptides; D044102:Receptor, Melanocortin, Type 1; C114880:trypsin-like serine protease; D000521:alpha-MSH; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone; D012697:Serine Endopeptidases