Melanin production through novel processing of proopiomelanocortin in the extracellular compartment of the auricular skin of C57BL/6 mice after UV-irradiation

作者：Yamamoto Hiroyuki^*; Yamane Tomohiro; Iguchi Kazuaki; Tanaka Kiyotaka; Iddamalgoda Arunasiri; Unno Keiko; Hoshino Minoru; Takeda Atsushi

来源：Scientific Reports, 2015, 5(1): 14579.

DOI：10.1038/srep14579

The production of melanin is regulated by alpha-melanocyte-stimulating hormone (alpha-MSH), which is produced from proopiomelanocortin (POMC). Keratinocytes release POMC along with lower levels of alpha-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 alpha-MSH-like immunoreactivity (alpha-MSH-LI) increased after UV-irradiation. However, other POMC-derived products were very low. In hypophysectomized mice, alpha-MSH-LI increased to the same level as in control mice after UV-irradiation. Structural analysis revealed that the major alpha-MSH-LI product was ACTH(1-8). Furthermore, ACTH(1-8) competed with [I-125]-alpha-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, alpha-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.

• 出版日期2015-9-29