UV‐induced DNA damage and melanin content in human skin differing in racial/ethnic origin

Tadokoro, Taketsugu; Kobayashi, Nobuhiko; Zmudzka, Barbara Z.; Itô, Shôsuke; Wakamatsu, Kazumasa; Yamaguchi, Yuji; Korossy, Katalin S.; Miller, Sharon A.; Beer, Janusz Z.; Hearing, Vincent J.

doi:10.1096/fj.02-0865fje

Cited by 319 publications

(350 citation statements)

References 40 publications

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“…The incidence and extent of these detrimental effects is largely dependent on the degree of constitutive pigmentation of the skin. [1][2][3][4][5][6] Human skin colour is determined by the total quantity of melanin, the proportion between the brown-black eumelanin and the yellow-red pheomelanin, and its distribution through the epidermis. [7][8][9] The type and amount of melanin is under the control of several genes with a great number of alleles, resulting in wide variations of skin colours.…”

Section: Discussionmentioning

confidence: 99%

Variations in skin colour and the biological consequences of ultraviolet radiation exposure

2013

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SummaryHarmful consequences of sun exposure range from sunburn, photoageing and pigmentary disorders to skin cancer. The incidence and extent of these detrimental effects are largely due to the degree of constitutive pigmentation of the skin. The latter can be objectively classified according to the individual typology angle (°ITA) based on colorimetric parameters. The physiological relevance of the ITA colorimetric classification was assessed in 3500 women living in various geographical areas. Furthermore, in order to understand the relationship between constitutive pigmentation and ultraviolet radiation (UVR) sensitivity, we worked on ex vivo human skin samples of different colour exposed to increasing UVR doses. For each sample we defined the biologically efficient dose (BED), based on the induction of sunburn cells, and analysed UVR-induced DNA damage (cyclobutane thymine dimers, CPD). We found a significant correlation between ITA and BED. We also found a correlation between ITA and DNA damage. As the epidermal basal layer also hosts melanocytes and in order to analyse the relationship between skin colour and DNA damage occurring specifically within this cell type, we performed double staining for CPD and tyrosinase-related protein (TRP) 1, a key enzyme in melanin synthesis. We found that DNA damage within melanocytes depends on ITA. Taken together our results may explain the higher risk of lighter skin types developing skin cancers, including melanoma, as well as the development of pigmentary disorders in moderately pigmented skin. They show that skin classification based on ITA is physiologically relevant (as it correlates with constitutive pigmentation) and further support the concept of a more personalized approach to photoprotection that corresponds to a particular skin colour type's sensitivity to solar UVR.What's already known about this topic?• Sun exposure sensitivity is largely dependent on the degree of skin constitutive pigmentation.What does this study add?• The individual typology angle (ITA)-based skin colour classification correlates with constitutive pigmentation and is physiologically relevant in different geographical areas.• It may help identify differential responses to ultraviolet radiation (UVR) exposure that correspond to particular skin colour type's UVR sensitivities.• It supports the concept of personalized photoprotection.Harmful consequences of sun exposure range from sunburn, photoageing and pigmentary disorders to skin cancer. The incidence and extent of these detrimental effects is largely dependent on the degree of constitutive pigmentation of the skin.1-6 Human skin colour is determined by the total quantity of melanin, the proportion between the brown-black eumelanin

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Section: Discussionmentioning

confidence: 99%

Variations in skin colour and the biological consequences of ultraviolet radiation exposure

2013

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“…Paraffin-embedded samples from human kidney, uterus, and lung were obtained from the tissue bank in Philadelphia. Shave biopsies, 4 mm in diameter, were taken before and 1 day after a 1 minimum erythema dose of UV radiation, as described previously (22).…”

Section: Methodsmentioning

confidence: 99%

Sialylated Core 1 O-Glycans Influence the Sorting of Pmel17/gp100 and Determine Its Capacity to Form Fibrils

Valencia

Rouzaud

Julien

et al. 2007

Journal of Biological Chemistry

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Pmel17 is a melanocyte/melanoma-specific protein that is essential for the maturation of melanosomes to form mature, fibrillar, and pigmented organelles. Recently, we reported that the less glycosylated form of Pmel17 (termed iPmel17) is sorted via the plasma membrane in a manner distinct from mature Pmel17 (termed mPmel17), which is sorted directly to melanosomes. To clarify the mechanism(s) underlying the distinct processing and sorting of Pmel17, we generated a highly specific antibody (termed ␣PEP25h) against an epitope within the repeat domain of Pmel17 that is sensitive to changes in O-glycosylation. ␣PEP25h recognizes only iPmel17 and allows analysis of the processing and sorting of iPmel17 when compared with ␣PEP13h, an antibody that recognizes both iPmel17 and mPmel17. Our novel findings using ␣PEP25h demonstrate that iPmel17 differs from mPmel17 not only in its sensitivity to endoglycosidase H, but also in the content of core 1 O-glycans modified with sialic acid. This evidence reveals that iPmel17 is glycosylated differently in the Golgi and that it is sorted through the secretory pathway. Analysis of Pmel17 processing in glycosylation-deficient mutant cells reveals that Pmel17 lacking the correct addition of sialic acid and galactose loses the ability to form fibrils. Furthermore, we show that addition of sialic acid affects the stability and sorting of Pmel17 and reduces pigmentation. Alterations in sialyltransferase activity and substrates differ between normal and transformed melanocytes and may represent a critical change during malignant transformation.The human PMEL17 gene encodes two type I integral membrane proteins that are translated from alternatively spliced mRNAs. Those two proteins, known as Pmel17 and gp100, differ as to whether they include a 7-amino acid motif in the membrane proximal region of the luminal domain (1-3). Pmel17 is critical to the formation of an internal fibrillar matrix within stage II melanosomes that is essential to the maturation of that organelle and the subsequent synthesis and deposition of melanin within it. Pmel17 is synthesized as a 68.6-kDa protein, as deduced from the cloned cDNA (2). It is rapidly and quantitatively glycosylated to an "immature" ϳ95-kDa form (termed iPmel17), but only a limited amount is further processed to a "mature" ϳ115-kDa form (termed mPmel17), due at least in part to N-glycosylation at five possible sites (4). mPmel17 can then be cleaved by a furin-like proprotein convertase that generates two fragments, one small fragment (cPmel17, ϳ26 kDa) containing the transmembrane (TM) 3 and the C-terminal domains, and the other larger fragment contains the N-terminal region (5). Those fragments can remain bound to each other by S-S bonds (5, 6). However, the iPmel17 formed remains fully endoglycosidase H (EndoH)-sensitive (4) and is significantly more stable over time than either of the other forms of Pmel17 (mPmel17 and cPmel17) (5).N-Linked core glycosylation begins in the ER and is essential for the function, stability, folding, intrace...

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“…the back or arms) is virtually identical in all types of skin (21). Keratinocytes in fair skin tend to cluster their poorly pigmented melanosomes above the nuclei, whereas in dark skin the heavily pigmented melanosomes are distributed individually in keratinocytes, thus maximizing their absorption of light (shown schematically in Fig.…”

Section: Regulation Of Constitutive Skin Pigmentationmentioning

confidence: 99%

The Regulation of Skin Pigmentation

Yamaguchi

Brenner

Hearing

2007

Journal of Biological Chemistry

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406

344

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Visible pigmentation of the skin, hair, and eyes depends primarily on the functions of melanocytes, a very minor population of cells that specialize in the synthesis and distribution of the pigmented biopolymer melanin. Melanocytes are derived from precursor cells (called melanoblasts) during embryological development, and melanoblasts destined for the skin originate from the neural crest. The accurate migration, distribution, and functioning of melanoblasts/melanocytes determine the visible phenotype of organisms ranging from simple fungi to the most complex animal species. In human skin, melanocytes are localized at the dermal/epidermal border in a characteristic regularly dispersed pattern. Each melanocyte at the basal layer of the epidermis is functionally connected to underlying fibroblasts in the dermis and to keratinocytes in the overlying epidermis. Those three types of cells are highly interactive and communicate with each other via secreted factors and their receptors and via cell/cell contacts to regulate the function and phenotype of the skin. Overview: Architecture of the SkinEpidermal melanocytes occur at an approximate ratio of 1:10 among basal keratinocytes and distribute the melanin they produce to ϳ40 overlying suprabasal keratinocytes via their elongated dendrites and cell/cell contacts (presented schematically in Fig. 1). Although melanocytes and stem cell keratinocytes in the basal layer of the epidermis are very stable populations that proliferate extremely slowly under normal circumstances, keratinocytes in the upper layers of the epidermis proliferate relatively rapidly. That upward pressure carries them toward the surface of the skin along with their ingested melanin to form a critical barrier for the organism against the environment and the many stresses that originate there. Thus it is not the melanin within melanocytes only, but in combination with the pigment in more superficial layers, that gives skin its characteristic color. Although melanocytes in other locations of the body (e.g. hair follicles, eyes, inner ear, etc.) interact with surrounding cells in manners distinct from those in the epidermis, the basic processes involved in producing the melanin and the organelles within which it is synthesized (termed melanosomes) are comparable, as are the factors that regulate melanogenesis. This review will restrict itself to epidermal pigmentation, and readers interested in factors influencing pigmentation at other sites should consult recent reviews (1-6) and books (7, 8) on those topics.

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UV‐induced DNA damage and melanin content in human skin differing in racial/ethnic origin

Cited by 319 publications

References 40 publications

Variations in skin colour and the biological consequences of ultraviolet radiation exposure

Variations in skin colour and the biological consequences of ultraviolet radiation exposure

Sialylated Core 1 O-Glycans Influence the Sorting of Pmel17/gp100 and Determine Its Capacity to Form Fibrils

The Regulation of Skin Pigmentation

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