Department of Chemistry, Fujita Health University School of Health Sciences, Aichi, Japan.
Department of Biophysics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
Photochem Photobiol. 2018 May;94(3):409-420. doi: 10.1111/php.12837. Epub 2017 Oct 26.
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 was employed to characterize 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) from the benzothiazine moiety of pheomelanin. The results 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). The TTCA/4-AHP ratio increases with photoaging, indicating the conversion of benzothiazine to the benzothiazole moiety. Analysis of those markers and their ratios show that both eumelanin and pheomelanin in human retinal pigment epithelium melanosomes undergo extensive structural modifications due to their lifelong exposure to blue light. Using synthetic melanins, we also found that singlet oxygen, in addition to superoxide anions, is photogenerated and quenched upon UVA irradiation. The (patho)physiological significance of those findings is discussed in relation to the tanning process, to melanomagenesis in the skin and to age-related macular degeneration in the eyes.
真黑素对有色组织有光保护作用，而褐黑素则有光毒性。在这篇综述中，我们总结了目前对真黑素和褐黑素结构如何被紫外线 A（UVA）以及可见光修饰的理解，以及活性氧物种如何参与这些过程。我们采用碱性过氧化氢氧化法对真黑素和苯并噻唑型褐黑素进行了表征，分别得到吡咯-2,3,5-三羧酸（PTCA）和噻唑-2,4,5-三羧酸（TTCA）。用氢碘酸进行还原水解，从褐黑素的苯并噻嗪部分得到 4-氨基-3-羟基苯丙氨酸（4-AHP）。结果表明，真黑素的光老化会产生游离的 PTCA（原位过氧化物产生）和吡咯-2,3,4,5-四羧酸（PTeCA，交联产生）。TTCA/4-AHP 比值随光老化而增加，表明苯并噻嗪向苯并噻唑部分的转化。对这些标志物及其比值的分析表明，由于人类视网膜色素上皮黑素小体中真黑素和褐黑素终生暴露在蓝光下，它们都经历了广泛的结构修饰。通过合成黑色素，我们还发现单线态氧，除了超氧阴离子外，在 UVA 照射下也会被光生成和淬灭。讨论了这些发现的（病理）生理学意义，涉及晒黑过程、皮肤黑素瘤发生和眼睛与年龄相关的黄斑变性。
