Oral Presentation 18th International Congress on Photobiology 2024

Photo-modification of Eumelanin and Pheomelanin and Its Biological Implications (#94)

Shosuke Ito 1
  1. Institute for Melanin Chemistry, Fujita Health University, Toyoake, AICHI, Japan

Melanocytes produce two types of pigment, eumelanin and pheomelanin. Eumelanin consists of 5,6-dihydroxyindole (DHI) and 5,6‐dihydroxyindole‐2‐carboxylic acid (DHICA), while pheomelanin consists of benzothiazine and benzothiazole units. It is generally accepted that eumelanin is photoprotective for pigmented tissues while pheomelanin is phototoxic. In this review, we summarize current understanding of how eumelanin and pheomelanin structures are modified by ultraviolet A (UVA) and also by visible light and how reactive oxygen species participate in those processes. Alkaline hydrogen peroxide oxidation (AHPO) was employed to characterize DHICA-derived eumelanin and benzothiazole-type pheomelanin, giving pyrrole-2,3,5-tricarboxylic acid (PTCA) and thiazole-2,4,5-tricarboxylic acid (TTCA), respectively. Reductive hydrolysis with hydroiodic acid gives 4-amino-3-hydroxyphenylalanine (4-AHP) and 3-AHP from the benzothiazine moiety of pheomelanin. Analyses of natural and synthetic melanins show that the photoaging of eumelanin gives rise to Free PTCA (produced by peroxidation in situ) and pyrrole-2,3,4,5-tetracarboxylic acid (PTeCA, produced by cross-linking), leading to the increases in the ratios of Free PTCA/Total PTCA and PTeCA/PTCA. In pheomelanin, the TTCA/4-AHP ratio increases and the 4-AHP/3-AHP ratio decreases with photoaging, indicating the conversion of benzothiazine to the benzothiazole moiety. Analysis of those markers and their ratios show that both eumelanin and pheomelanin are photo-modified in human hair, alpaca fiber, cultured melanocytes, human retinal pigment epithelium melanosomes, and human ex vivo skin. Using synthetic melanins, we also found that singlet oxygen, in addition to superoxide anions, is photogenerated and quenched upon UVA irradiation. The biological implications of those findings are discussed in relation to the tanning process, to melanomagenesis in the skin and to age-related macular degeneration in the eyes.