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The Keio Journal of Medicine Mar 1995Certain aspects of current progress in melanin biology and its possible clinical relevances are reviewed with emphasis on some of our recent research activities. The... (Review)
Review
Certain aspects of current progress in melanin biology and its possible clinical relevances are reviewed with emphasis on some of our recent research activities. The important aspects discussed are (a) the biological properties of melanin pigments and their relevance to biological functions, (b) functional interaction of melanogenic/melanogenesis-associated genes in melanin biosynthesis process (melanogenesis, and (c) the targeting of proteins involved in melanogenesis and assembly by melanosomal proteins. Upon exposure to UV light radiation (UVR), melanin pigments revealed two distinct photobiological reactions, i.e. photoprotective and phototoxic reactions. The precursor intermediate of brown-black eumelanin, 5-6-dihydroxyindole, appears to possess the most potent photoprotective (antioxidant) property. Eumelanin pigment also had some antioxidant property. Similarly, yellow-red pheomelanin and its precursor intermediate, 5-S-cysteinyldopa also revealed some antioxidant property, but they became prooxidant in the presence of the ferric iron upon exposure to UVR. Melanosomes are known to possess several metal ions including Fe2+, Fe3+, Cu2+ and Zn2+. In addition, upon exposure to UV-light, there is an increase in ferric/ferrous iron in the skin. Therefore, in the in vivo system, pheomelanin intermediate, 5-S-cysteinyldopa, may show significant prooxidant property in conjunction with metal ions (e.g. Fe2+, Fe3+). When atypical moles (previously called dysplastic nevi) were analysed chemically for quantitative and qualitative properties of melanin pigment, they revealed a high ratio of pheomelanin/eumelanin content. This finding may partly explain our clinical observation that these moles are frequently the precursors of malignant melanoma and that the intermittent heavy exposure of UVR can be the major direct cause of their transformation. How, then, the melanosomal compartment, where active new melanin synthesis occurs after exposure to UVR, is protected from the cytotoxicity of melanin precursor intermediates. To study this question, two major experiments were conducted; (a) expression of melanogenesis-associated genes upon exposure of melanocytes to UVR and (b) transfection of cDNAs from the melanogenesis-associated genes. There was coordinated gene expression (mRNA) of tyrosinase and tyrosinase-related protein, TRP-1 and this coordinated gene expression was also accompanied by the upregulation of LAMP-1 (lysosome-associated membrane protein-1). Furthermore, human tyrosinase and TRP-1 mRNAs were expressed successfully in individual transfectants or co-transfectants of cDNAs from the two genes. Co-transfectants of human tyrosinase and TRP-1 cDNAs produced many lysosomal granules and melanin-containing granules, melanosomes. LAMP-1 gene was upregulated simultaneously in co-transfectants of tyrosinase and TRP-1, but not in individual transfectants of the two genes.(ABSTRACT TRUNCATED AT 400 WORDS)
Topics: Forecasting; Humans; Melanins; Skin Pigmentation
PubMed: 7760535
DOI: 10.2302/kjm.44.9 -
Applied Microbiology and Biotechnology Feb 2012Melanin is a unique pigment with myriad functions that is found in all biological kingdoms. It is multifunctional, providing defense against environmental stresses such... (Review)
Review
Melanin is a unique pigment with myriad functions that is found in all biological kingdoms. It is multifunctional, providing defense against environmental stresses such as ultraviolet (UV) light, oxidizing agents and ionizing radiation. Melanin contributes to the ability of fungi to survive in harsh environments. In addition, it plays a role in fungal pathogenesis. Melanin is an amorphous polymer that is produced by one of two synthetic pathways. Fungi may synthesize melanin from endogenous substrate via a 1,8-dihydroxynaphthalene (DHN) intermediate. Alternatively, some fungi produce melanin from L-3,4-dihydroxyphenylalanine (L-dopa). The detailed chemical structure of melanin is not known. However, microscopic studies show that it has an overall granular structure. In fungi, melanin granules are localized to the cell wall where they are likely cross-linked to polysaccharides. Recent studies suggest the fungal melanin may be synthesized in internal vesicles akin to mammalian melanosomes and transported to the cell wall. Potential applications of melanin take advantage of melanin's radioprotective properties and propensity to bind to a variety of substances.
Topics: Cell Wall; Cryptococcus neoformans; Fungi; Melanins; Melanosomes; Microscopy, Electron, Transmission
PubMed: 22173481
DOI: 10.1007/s00253-011-3777-2 -
International Journal of Molecular... Jul 2017The huge development of bioengineering during the last years has boosted the search for new bioinspired materials, with tunable chemical, mechanical, and optoelectronic... (Review)
Review
The huge development of bioengineering during the last years has boosted the search for new bioinspired materials, with tunable chemical, mechanical, and optoelectronic properties for the design of semiconductors, batteries, biosensors, imaging and therapy probes, adhesive hydrogels, tissue restoration, photoprotectors, etc. These new materials should complement or replace metallic or organic polymers that cause cytotoxicity and some adverse health effects. One of the most interesting biomaterials is melanin and synthetic melanin-related molecules. Melanin has a controversial molecular structure, dependent on the conditions of polymerization, and therefore tunable. It is found in animal hair and skin, although one of the common sources is cuttlefish (Sepia officinalis) ink. On the other hand, mussels synthesize adhesive proteins to anchor these marine animals to wet surfaces. Both melanin and mussel foot proteins contain a high number of catecholic residues, and their properties are related to these groups. Dopamine (DA) can easily polymerize to get polydopamine melanin (PDAM), that somehow shares properties with melanin and mussel proteins. Furthermore, PDAM can easily be conjugated with other components. This review accounts for the main aspects of melanin, as well as DA-based melanin-like materials, related to their biomedical and biotechnological applications.
Topics: Animals; Biomedical Technology; Biomimetics; Biotechnology; Bivalvia; Melanins; Polymers; Sepia
PubMed: 28718807
DOI: 10.3390/ijms18071561 -
International Journal of Cosmetic... Aug 2008Skin and hair colour contribute significantly to our overall visual appearance and to social/sexual communication. Despite their shared origins in the embryologic neural... (Review)
Review
Skin and hair colour contribute significantly to our overall visual appearance and to social/sexual communication. Despite their shared origins in the embryologic neural crest, the hair follicle and epidermal pigmentary units occupy distinct, although open, cutaneous compartments. They can be distinguished principally on the basis of the former's stringent coupling to the hair growth cycle compared with the latter's continuous melanogenesis. The biosynthesis of melanin and its subsequent transfer from melanocyte to hair bulb keratinocytes depend on the availability of melanin precursors and on a raft of signal transduction pathways that are both highly complex and commonly redundant. These signalling pathways can be both dependent and independent of receptors, act through auto-, para- or intracrine mechanisms and can be modified by hormonal signals. Despite many shared features, follicular melanocytes appear to be more sensitive than epidermal melanocytes to ageing influences. This can be seen most dramatically in hair greying/canities and this is likely to reflect significant differences in the epidermal and follicular microenvironments. The hair follicle pigmentary unit may also serve as an important environmental sensor, whereby hair pigment contributes to the rapid excretion of heavy metals, chemicals and toxins from the body by their selective binding to melanin; rendering the hair fibre a useful barometer of exposures. The recent availability of advanced cell culture methodologies for isolated hair follicle melanocytes and for intact anagen hair follicle organ culture should provide the research tools necessary to elucidate the regulatory mechanisms of hair follicle pigmentation. In the longer term, it may be feasible to develop hair colour modifiers of a biological nature to accompany those based on chemicals.
Topics: Hair Color; Hair Follicle; Humans; Melanins; Melanocytes
PubMed: 18713071
DOI: 10.1111/j.1468-2494.2008.00456.x -
International Journal of Molecular... May 2023The melanin pigments eumelanin (EM) and pheomelanin (PM), which are dark brown to black and yellow to reddish-brown, respectively, are widely found among vertebrates.... (Review)
Review
The melanin pigments eumelanin (EM) and pheomelanin (PM), which are dark brown to black and yellow to reddish-brown, respectively, are widely found among vertebrates. They are produced in melanocytes in the epidermis, hair follicles, the choroid, the iris, the inner ear, and other tissues. The diversity of colors in animals is mainly caused by the quantity and quality of their melanin, such as by the ratios of EM versus PM. We have developed micro-analytical methods to simultaneously measure EM and PM and used these to study the biochemical and genetic fundamentals of pigmentation. The photoreactivity of melanin has become a major focus of research because of the postulated relevance of EM and PM for the risk of UVA-induced melanoma. Our biochemical methods have found application in many clinical studies on genetic conditions associated with alterations in pigmentation. Recently, besides chemical degradative methods, other methods have been developed for the characterization of melanin, and these are also discussed here.
Topics: Animals; Melanins; Melanocytes; Pigmentation; Epidermis; Melanoma
PubMed: 37176019
DOI: 10.3390/ijms24098305 -
Cells Jun 2022Melanosomes are melanocyte-specific organelles that protect cells from ultraviolet (UV)-induced deoxyribonucleic acid damage through the production and accumulation of... (Review)
Review
Melanosomes are melanocyte-specific organelles that protect cells from ultraviolet (UV)-induced deoxyribonucleic acid damage through the production and accumulation of melanin and are transferred from melanocytes to keratinocytes. The relatively well-known process by which melanin is synthesized from melanocytes is known as melanogenesis. The relationship between melanogenesis and autophagy is attracting the attention of researchers because proteins associated with autophagy, such as WD repeat domain phosphoinositide-interacting protein 1, microtubule-associated protein 1 light chain 3, autophagy-related (ATG)7, ATG4, beclin-1, and UV-radiation resistance-associated gene, contribute to the melanogenesis signaling pathway. Additionally, there are reports that some compounds used as whitening cosmetics materials induce skin depigmentation through autophagy. Thus, the possibility that autophagy is involved in the removal of melanin has been suggested. To date, however, there is a lack of data on melanosome autophagy and its underlying mechanism. This review highlights the importance of autophagy in melanin homeostasis by providing an overview of melanogenesis, autophagy, the autophagy machinery involved in melanogenesis, and natural compounds that induce autophagy-mediated depigmentation.
Topics: Autophagy; Homeostasis; Melanins; Melanocytes; Melanosomes
PubMed: 35805169
DOI: 10.3390/cells11132085 -
Experimental Eye Research Sep 2014The retinal pigment epithelium contains three major types of pigment granules; melanosomes, lipofuscin and melanolipofuscin. Melanosomes in the retinal pigment... (Review)
Review
The retinal pigment epithelium contains three major types of pigment granules; melanosomes, lipofuscin and melanolipofuscin. Melanosomes in the retinal pigment epithelium (RPE) are formed during embryogenesis and mature during early postnatal life while lipofuscin and melanolipofuscin granules accumulate as a function of age. The difficulty in studying the formation and consequences of melanosomes and lipofuscin granules in RPE cell culture is compounded by the fact that these pigment granules do not normally occur in established RPE cell lines and pigment granules are rapidly lost in adult human primary culture. This review will consider options available for overcoming these limitations and permitting the study of melanosomes and lipofuscin in cell culture and will briefly evaluate the advantages and disadvantages of the different protocols.
Topics: Animals; Cells, Cultured; Epithelial Cells; Humans; Lipofuscin; Melanins; Models, Animal; Models, Biological; Retinal Pigment Epithelium
PubMed: 25152361
DOI: 10.1016/j.exer.2014.01.016 -
Proceedings. Biological Sciences Aug 2015Colour, derived primarily from melanin and/or carotenoid pigments, is integral to many aspects of behaviour in living vertebrates, including social signalling, sexual... (Review)
Review
Colour, derived primarily from melanin and/or carotenoid pigments, is integral to many aspects of behaviour in living vertebrates, including social signalling, sexual display and crypsis. Thus, identifying biochromes in extinct animals can shed light on the acquisition and evolution of these biological traits. Both eumelanin and melanin-containing cellular organelles (melanosomes) are preserved in fossils, but recognizing traces of ancient melanin-based coloration is fraught with interpretative ambiguity, especially when observations are based on morphological evidence alone. Assigning microbodies (or, more often reported, their 'mouldic impressions') as melanosome traces without adequately excluding a bacterial origin is also problematic because microbes are pervasive and intimately involved in organismal degradation. Additionally, some forms synthesize melanin. In this review, we survey both vertebrate and microbial melanization, and explore the conflicts influencing assessment of microbodies preserved in association with ancient animal soft tissues. We discuss the types of data used to interpret fossil melanosomes and evaluate whether these are sufficient for definitive diagnosis. Finally, we outline an integrated morphological and geochemical approach for detecting endogenous pigment remains and associated microstructures in multimillion-year-old fossils.
Topics: Animals; Biological Evolution; Fossils; Melanins; Melanosomes; Microbodies; Pigmentation; Vertebrates
PubMed: 26290071
DOI: 10.1098/rspb.2015.0614 -
International Journal of Molecular... Apr 2016The regulation of melanin production is important for managing skin darkness and hyperpigmentary disorders. Numerous anti-melanogenic agents that target tyrosinase... (Review)
Review
The regulation of melanin production is important for managing skin darkness and hyperpigmentary disorders. Numerous anti-melanogenic agents that target tyrosinase activity/stability, melanosome maturation/transfer, or melanogenesis-related signaling pathways have been developed. As a rate-limiting enzyme in melanogenesis, tyrosinase has been the most attractive target, but tyrosinase-targeted treatments still pose serious potential risks, indicating the necessity of developing lower-risk anti-melanogenic agents. Sugars are ubiquitous natural compounds found in humans and other organisms. Here, we review the recent advances in research on the roles of sugars and sugar-related agents in melanogenesis and in the development of sugar-based anti-melanogenic agents. The proposed mechanisms of action of these agents include: (a) (natural sugars) disturbing proper melanosome maturation by inducing osmotic stress and inhibiting the PI3 kinase pathway and (b) (sugar derivatives) inhibiting tyrosinase maturation by blocking N-glycosylation. Finally, we propose an alternative strategy for developing anti-melanogenic sugars that theoretically reduce melanosomal pH by inhibiting a sucrose transporter and reduce tyrosinase activity by inhibiting copper incorporation into an active site. These studies provide evidence of the utility of sugar-based anti-melanogenic agents in managing skin darkness and curing pigmentary disorders and suggest a future direction for the development of physiologically favorable anti-melanogenic agents.
Topics: Animals; Antigens, Neoplasm; Carbohydrates; Humans; Melanins; Membrane Transport Proteins; Skin Pigmentation
PubMed: 27092497
DOI: 10.3390/ijms17040583 -
FEBS Open Bio Apr 2019Melanin-producing and are highly invasive and can suppress or escape the immune system of the host. Since non-melanin-producing strains do not affect the immune...
Melanin-producing and are highly invasive and can suppress or escape the immune system of the host. Since non-melanin-producing strains do not affect the immune system, melanin may play a role in immune system suppression. Artificial melanin synthesized using conventional methods is insoluble, making structural and functional analysis of this chemical difficult. In this study, we describe a melanin solubilization method based on polymerization of homogentisic acid (solubilizing component) and an equivalent amount of L-DOPA in the presence of laccase. In addition, we investigated the effect of melanin on the immune system. Homogentisic acid and L-DOPA mixed melanin (HALD), the synthetic solubilized melanin, did not exert a cytotoxic effect on mouse macrophages. HALD suppressed cytokine and reactive oxygen species production by macrophages when they were stimulated by fungal components. HALD also suppressed the phagocytosis of fungal components by macrophages. These results suggest that HALD can suppress the function of macrophages without causing cytotoxicity.
Topics: Animals; Biochemistry; Homogentisic Acid; Laccase; Levodopa; Macrophages; Male; Melanins; Mice; Mice, Inbred C57BL; Polymerization; Solubility
PubMed: 30984552
DOI: 10.1002/2211-5463.12615