Variation in Melanin Content and Composition in Type V and VI Photoexposed and Photoprotected Human Skin: The Dominant Role of DHI

Abstract

A combination of techniques, including high-performance liquid chromatography (HPLC), spectrophotometric measurements, and a novel method for quantifying melanosome morphology, were applied to the analysis of melanin content and composition in highly pigmented (Fitzpatrick type V and VI) human skin. We found that total epidermal melanin content is significantly elevated in photoexposed type V and VI skin (approximately 1.6 x), while analysis of individual melanin components suggests that pheomelanin content increases only slightly, whereas 5,6-dihydroxyindole-2-carboxylic acid (DHICA)-eumelanin and to a greater extent 5,6-dihydroxyindole (DHI)-eumelanin content are both markedly elevated. Analysis of the relative composition of epidermal melanin in these subjects revealed that DHI-eumelanin is the largest single component (approximately 60-70%), followed by DHICA-eumelanin (25-35%), with pheomelanin being a relatively minor component (2-8%). Moreover, there was a comparative enrichment of DHI-eumelanin at photoexposed sites, with a corresponding decline in the relative contributions from DHICA-eumelanin and pheomelanin. There was also a good correlation and close agreement between the concentration of spheroidal melanosomes determined by morphological image analysis and the concentration of pheomelanin determined by a combination of HPLC and spectrophotometric analysis (r = 0.89, P < 0.02). This study demonstrates the usefulness of melanosome morphology analysis as a sensitive new method for the quantification of melanin composition in human skin. The data also suggest that DHI-eumelanin formation is the dominant pathway for melanin synthesis in heavily pigmented (Fitzpatrick V and VI) skin types in vivo, and is the favoured pathway when melanin production is increased in chronically photoexposed skin.

Genetic variants in pigmentation genes, pigmentary phenotypes, and risk of skin cancer in Caucasians

“…Another limitation of our study was that we used self-reported pigmentary phenotypes. Such assessment may miss certain aspects of pigmentary phenotypes influenced by these genetic variants, such as melanin content and composition 64, 65. In addition, misclassification is always a concern in epidemiologic studies.…”

Differential Antifungal Activity of Human and Cryptococcal Melanins with Structural Discrepancies

“…In human beings this pigment is made up of three different components: pheomelanin, of light yellow or red color, soluble in alkali; eumelanin rich in 5.6-dihidroxiindol-2-carboxylic acid (DHICA), of light brown color, soluble in alkali and eumelanin rich in 5,6-dihydroxiindole (DHI) of dark brown or black color. Thus, the wide range of skin tones and human hair are therefore the result of various combinations of the impact of those three factors (Alaluf et al, 2001). Preliminary studies in our laboratory demonstrated that commercial synthetic melanin (Sigma–Aldrich TM ) had an antifungal activity against Candida albicans and other Candida species, such as C. parapsilosis strain 22019, C. glabrata strain 2001, C. krusei strain 6258 (Fuentes et al, 2014).…”

Ethnic skin types: are there differences in skin structure and function?1

“…There is also a highly significant correlation between the concentrations of spherical melanosomes and pheomelanin [13]. Examining other racial types Alaluf et al [14,15] demonstrated that the most lightly pigmented types (European, Chinese and Mexican) have approximately half as much epidermal melanin as the most darkly pigmented skin types (African and Indian). However, the composition of the lighter skin types was comparatively more enriched with lightly colored alkali soluble melanin components (3·).…”