International Journal of Molecular Sciences

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3 pages, 172 KiB

Open AccessEditorial

Skin Pigmentation: Is the Control of Melanogenesis a Target within Reach?

by Alessandra Napolitano and Shosuke Ito

Int. J. Mol. Sci. 2018, 19(12), 4040; https://doi.org/10.3390/ijms19124040 - 14 Dec 2018

Cited by 5 | Viewed by 3316

Abstract

Skin pigmentation represents one of the most peculiar traits of human beings and its alteration as a consequence of pathological conditions has a dramatic impact on the wellness of individuals and their social relationships. [...] Full article

(This article belongs to the Special Issue Melanins and Melanogenesis: From Nature to Applications)

Research

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10 pages, 1842 KiB

Open AccessArticle

Pulsed Electromagnetic Fields Increase Pigmentation through the p-ERK/p-p38 Pathway in Zebrafish (Danio rerio)

by Yu-Mi Kim, Han-Moi Lim, Hyang-Seon Ro, Ga-Eun Ki and Young-Kwon Seo

Int. J. Mol. Sci. 2018, 19(10), 3211; https://doi.org/10.3390/ijms19103211 - 17 Oct 2018

Cited by 13 | Viewed by 4540

Abstract

Melanogenesis is a biological process resulting in the production of melanin pigment, which plays an important role in the prevention of sun-induced skin injury, and determines hair and skin color. So, a wide variety of approaches have been proposed to increase the synthesis [...] Read more.

Melanogenesis is a biological process resulting in the production of melanin pigment, which plays an important role in the prevention of sun-induced skin injury, and determines hair and skin color. So, a wide variety of approaches have been proposed to increase the synthesis of melanin. This study evaluated the effects of pulsed electromagnetic fields (PEMFs) on the pigmentation of zebrafish (Danio rerio) in vivo. We stimulated pigmentation in zebrafish by using specific frequencies and intensities of PEMFs. This study focuses on pigmentation using PEMFs, and finds that PEMFs, at an optimal intensity and frequency, upregulate pigmentation by the stimulated expression of tyrosinase-related protein 1 (TRP1), dopachrome tautomerase (DCT) through extracellular signal-regulated kinase(ERK) phosphorylation, and p38 phosphorylation signaling pathways in zebrafish. These results suggest that PEMFs, at an optimal intensity and frequency, are a useful tool in treating gray hair, with reduced melanin synthesis in the hair shaft or hypopigmentation-related skin disorders. Full article

(This article belongs to the Special Issue Melanins and Melanogenesis: From Nature to Applications)

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17 pages, 2314 KiB

Open AccessArticle

Zerumbone, a Tropical Ginger Sesquiterpene of Zingiber officinale Roscoe, Attenuates α-MSH-Induced Melanogenesis in B16F10 Cells

by Taek-In Oh, Hye-Jeong Jung, Yoon-Mi Lee, Sujin Lee, Geon-Hee Kim, Sang-Yeon Kan, Hyeji Kang, Taerim Oh, Hyun Myung Ko, Keun-Chang Kwak and Ji-Hong Lim

Int. J. Mol. Sci. 2018, 19(10), 3149; https://doi.org/10.3390/ijms19103149 - 13 Oct 2018

Cited by 29 | Viewed by 8036

Abstract

Zerumbone (ZER), an active constituent of the Zingiberaceae family, has been shown to exhibit several biological activities, such as anti-inflammatory, anti-allergic, anti-microbial, and anti-cancer; however, it has not been studied for anti-melanogenic properties. In the present study, we demonstrate that ZER and Zingiber [...] Read more.

Zerumbone (ZER), an active constituent of the Zingiberaceae family, has been shown to exhibit several biological activities, such as anti-inflammatory, anti-allergic, anti-microbial, and anti-cancer; however, it has not been studied for anti-melanogenic properties. In the present study, we demonstrate that ZER and Zingiber officinale (ZO) extract significantly attenuate melanin accumulation in α-melanocyte-stimulating hormone (α-MSH)-stimulated mouse melanogenic B16F10 cells. Further, to elucidate the molecular mechanism by which ZER suppresses melanin accumulation, we analyzed the expression of melanogenesis-associated transcription factor, microphthalmia-associated transcription factor (MITF), and its target genes, such as tyrosinase, tyrosinase-related protein 1 (TYRP1), and tyrosinase-related protein 2 (TYRP2), in B16F10 cells that are stimulated by α-MSH. Here, we found that ZER inhibits the MITF-mediated expression of melanogenic genes upon α-MSH stimulation. Additionally, cells treated with different concentrations of zerumbone and ZO showed increased extracellular signal-regulated kinases 1 and 2 (ERK1/2) phosphorylation, which are involved in the degradation mechanism of MITF. Pharmacological inhibition of ERK1/2 using U0126 sufficiently reversed the anti-melanogenic effect of ZER, suggesting that increased phosphorylation of ERK1/2 is required for its anti-melanogenic activity. Taken together, these results suggest that ZER and ZO extract can be used as active ingredients in skin-whitening cosmetics because of their anti-melanogenic effect. Full article

(This article belongs to the Special Issue Melanins and Melanogenesis: From Nature to Applications)

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15 pages, 5963 KiB

Open AccessArticle

Antimelanogenic Effects of Polygonum tinctorium Flower Extract from Traditional Jeju Fermentation via Upregulation of Extracellular Signal-Regulated Kinase and Protein Kinase B Activation

by You Chul Chung, Ji-Hye Ko, Hyun-Kyu Kang, Seoyeon Kim, Choon Il Kang, Jung No Lee, Sung-Min Park and Chang-Gu Hyun

Int. J. Mol. Sci. 2018, 19(10), 2895; https://doi.org/10.3390/ijms19102895 - 24 Sep 2018

Cited by 22 | Viewed by 4596

Abstract

This study was carried out to investigate the antimelanogenic effects of a Polygonum tinctorium flower extract obtained using red nuruk, a traditional Jeju barley-based fermentation starter. We also studied the mechanism of action of the P. tinctorium fermented flower extract (PTFFE) in mouse [...] Read more.

This study was carried out to investigate the antimelanogenic effects of a Polygonum tinctorium flower extract obtained using red nuruk, a traditional Jeju barley-based fermentation starter. We also studied the mechanism of action of the P. tinctorium fermented flower extract (PTFFE) in mouse melanoma cells (B16F10). Cells were treated with various concentrations (62.5, 125 and 250 μg/mL) of PTFFE and the results showed that PTFFE significantly decreased the melanin content and tyrosinase activity without being cytotoxic. In addition, PTFFE strongly inhibited the expression of tyrosinase and tyrosinase-related protein 2 by decreasing the expression of the microphthalmia-associated transcription factor, as shown by a western blot assay. Furthermore, PTFFE inhibited melanogenesis via upregulation of the phosphorylation of extracellular signal-regulated kinase (ERK) and protein kinase B, also known as AKT. We also used inhibitors such as PD98059 (a specific ERK inhibitor) or LY294002 (an AKT inhibitor) to determine whether the signaling pathways are involved. High-performance liquid chromatography fingerprinting showed the presence of a quercetin glucoside (isoquercitrin) and quercetin in PTFFE. To test the potential for PTFFE application as a cosmetic material, we also performed a primary skin irritation test on human skin. In this assay, PTFFE did not induce any adverse reactions at the treatment dose. Based on these results, we suggest that PTFFE may be considered a potential antimelanogenesis candidate for topical applications. Full article

(This article belongs to the Special Issue Melanins and Melanogenesis: From Nature to Applications)

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14 pages, 1682 KiB

Open AccessArticle

Conjugation with Dihydrolipoic Acid Imparts Caffeic Acid Ester Potent Inhibitory Effect on Dopa Oxidase Activity of Human Tyrosinase

by Raffaella Micillo, Julia Sirés-Campos, José Carlos García-Borrón, Lucia Panzella, Alessandra Napolitano and Conchi Olivares

Int. J. Mol. Sci. 2018, 19(8), 2156; https://doi.org/10.3390/ijms19082156 - 24 Jul 2018

Cited by 14 | Viewed by 5188

Abstract

Caffeic acid derivatives represent promising lead compounds in the search for tyrosinase inhibitors to be used in the treatment of skin local hyperpigmentation associated to an overproduction or accumulation of melanin. We recently reported the marked inhibitory activity of a conjugate of caffeic [...] Read more.

Caffeic acid derivatives represent promising lead compounds in the search for tyrosinase inhibitors to be used in the treatment of skin local hyperpigmentation associated to an overproduction or accumulation of melanin. We recently reported the marked inhibitory activity of a conjugate of caffeic acid with dihydrolipoic acid, 2-S-lipoylcaffeic acid (LCA), on the tyrosine hydroxylase (TH) and dopa oxidase (DO) activities of mushroom tyrosinase. In the present study, we evaluated a more lipophilic derivative, 2-S-lipoyl caffeic acid methyl ester (LCAME), as an inhibitor of tyrosinase from human melanoma cells. Preliminary analysis of the effects of LCAME on mushroom tyrosinase indicated more potent inhibitory effects on either enzyme activities (IC₅₀ = 0.05 ± 0.01 μM for DO and 0.83 ± 0.09 μM for TH) compared with LCA and the reference compound kojic acid. The inhibition of DO of human tyrosinase was effective (Ki = 34.7 ± 1.1 μM) as well, while the action on TH was weaker. Lineweaver–Burk analyses indicated a competitive inhibitor mechanism. LCAME was not substrate of tyrosinase and proved nontoxic at concentrations up to 50 μM. No alteration of basal tyrosinase expression was observed after 24 h treatment of human melanoma cells with the inhibitor, but preliminary evidence suggested LCAME might impair the induction of tyrosinase expression in cells stimulated with α-melanocyte-stimulating hormone. All these data point to this compound as a valuable candidate for further trials toward its use as a skin depigmenting agent. They also highlight the differential effects of tyrosinase inhibitors on the human and mushroom enzymes. Full article

(This article belongs to the Special Issue Melanins and Melanogenesis: From Nature to Applications)

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22 pages, 15912 KiB

Open AccessArticle

Structural Requirements of Alkylglyceryl-l-Ascorbic Acid Derivatives for Melanogenesis Inhibitory Activity

by Norihisa Taira, Yushi Katsuyama, Masato Yoshioka, Osamu Muraoka and Toshio Morikawa

Int. J. Mol. Sci. 2018, 19(4), 1144; https://doi.org/10.3390/ijms19041144 - 10 Apr 2018

Cited by 10 | Viewed by 8082

Abstract

l-Ascorbic acid has multifunctional benefits on skin aesthetics, including inhibition of melanin production, and is widely used in cosmetics. It, however, has low stability and poor skin penetration. We hypothesize that alkylglyceryl-l-ascorbic acid derivatives, highly stable vitamin C–alkylglycerol conjugates, would [...] Read more.

l-Ascorbic acid has multifunctional benefits on skin aesthetics, including inhibition of melanin production, and is widely used in cosmetics. It, however, has low stability and poor skin penetration. We hypothesize that alkylglyceryl-l-ascorbic acid derivatives, highly stable vitamin C–alkylglycerol conjugates, would have similar anti-melanogenic activity with better stability and penetration. We test 28 alkylglyceryl-l-ascorbic acid derivatives (1–28) on theophylline-stimulated B16 melanoma 4A5 cells to determine if they inhibit melanogenesis and establish any structure–function relationships. Although not the most potent inhibitors, 3-O-(2,3-dihydroxypropyl)-2-O-hexyl-l-ascorbic acid (6, IC₅₀ = 81.4 µM) and 2-O-(2,3-dihydroxypropyl)-3-O-hexyl-l-ascorbic acid (20, IC₅₀ = 117 µM) are deemed the best candidate derivatives based on their inhibitory activities and low toxicities. These derivatives are also found to be more stable than l-ascorbic acid and to have favorable characteristics for skin penetration. The following structural requirements for inhibitory activity of alkylglyceryl-l-ascorbic acid derivatives are also determined: (i) alkylation of glyceryl-l-ascorbic acid is essential for inhibitory activity; (ii) the 3-O-alkyl-derivatives (2–14) exhibit stronger inhibitory activity than the corresponding 2-O-alkyl-derivatives (16–28); and (iii) derivatives with longer alkyl chains have stronger inhibitory activities. Mechanistically, our studies suggest that l-ascorbic acid derivatives exert their effects by suppressing the mRNA expression of tyrosinase and tyrosine-related protein-1. Full article

(This article belongs to the Special Issue Melanins and Melanogenesis: From Nature to Applications)

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14 pages, 14760 KiB

Open AccessArticle

Sesamol Inhibited Melanogenesis by Regulating Melanin-Related Signal Transduction in B16F10 Cells

by Po-Yuan Wu, Ya-Jhen You, Yi-Jung Liu, Chien-Wei Hou, Chin-Sheng Wu, Kuo-Ching Wen, Chien-Yih Lin and Hsiu-Mei Chiang

Int. J. Mol. Sci. 2018, 19(4), 1108; https://doi.org/10.3390/ijms19041108 - 7 Apr 2018

Cited by 48 | Viewed by 9602

Abstract

Melanin is synthesized through a series of interactions catalyzed by melanogenic enzymes such as tyrosinase, dopachrome tautomerase (tyrosinase-related protein-2; TRP-2), and tyrosinase-related protein-1 (TRP-1). Tyrosinase plays a key role in catalysing the initial and limiting steps of melanogenesis. The melanin that results from [...] Read more.

Melanin is synthesized through a series of interactions catalyzed by melanogenic enzymes such as tyrosinase, dopachrome tautomerase (tyrosinase-related protein-2; TRP-2), and tyrosinase-related protein-1 (TRP-1). Tyrosinase plays a key role in catalysing the initial and limiting steps of melanogenesis. The melanin that results from melanogenesis has the protective effect of absorbing ultraviolet radiation. However, overproduction of melanin, in addition to altering the appearance of skin, may lead to skin disorders such as melasma, solar lentigo, and postinflammatory hyperpigmentation. Previous studies have revealed that sesamol is a strong antioxidant and a free radical scavenger. In this study, we investigated the effects of sesamol on the regulation of melanogenesis and related mechanisms in B16F10 cells. The results indicated that sesamol inhibited tyrosinase activity and melanogenesis induced by α-melanocyte-stimulating hormone (α-MSH) in B16F10 melanoma cells. Sesamol decreased the protein level of melanocortin 1 receptor (MC1R), microphthalmia-associated transcription factor (MITF), tyrosinase, and TRP-1 by downregulating cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) pathways that had been activated by α-MSH. Sesamol increased glycogen synthase kinase 3 beta (GSK3β), protein kinase B (AKT), and extracellular signal-related kinase (ERK) phosphorylation, thus inhibiting the transcription of MITF. Sesamol also inhibited melanin synthesis and tyrosinase expression by modulating ERK, phosphoinositide 3-kinase (PI3K)/AKT, p38, and c-Jun amino-terminal kinase (JNK) signalling pathways. These results indicate that sesamol acted as a potent depigmenting agent. Full article

(This article belongs to the Special Issue Melanins and Melanogenesis: From Nature to Applications)

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12 pages, 8877 KiB

Open AccessArticle

Novel (1E,3E,5E)-1,6-bis(Substituted phenyl)hexa-1,3,5-triene Analogs Inhibit Melanogenesis in B16F10 Cells and Zebrafish

by Jisun Oh, Jungeun Kim, Jin Ho Jang, Sangwoo Lee, Chul Min Park, Woo-Keun Kim and Jong-Sang Kim

Int. J. Mol. Sci. 2018, 19(4), 1067; https://doi.org/10.3390/ijms19041067 - 3 Apr 2018

Cited by 10 | Viewed by 4976

Abstract

The present study aimed to evaluate the anti-melanogenic activity of 1,6-diphenyl-1,3,5-hexatriene and its derivatives in B16F10 murine melanoma cells and zebrafish embryos. Twenty five (1E,3E,5E)-1,6-bis(substituted phenyl)hexa-1,3,5-triene analogs were synthesized and their non-cytotoxic effects were predictively [...] Read more.

The present study aimed to evaluate the anti-melanogenic activity of 1,6-diphenyl-1,3,5-hexatriene and its derivatives in B16F10 murine melanoma cells and zebrafish embryos. Twenty five (1E,3E,5E)-1,6-bis(substituted phenyl)hexa-1,3,5-triene analogs were synthesized and their non-cytotoxic effects were predictively analyzed using three-dimensional quantitative structure-activity relationship approach. Inhibitory activities of these synthetic compounds against melanin synthesis were determined by evaluating melanin content and melanogenic regulatory enzyme expression in B16F10 cells. The anti-melanogenic activity was verified by observing body pigmentation in zebrafishes treated with these compounds. Compound #2, #4, and #6 effectively decreased melanogenesis induced by α-melanocyte-stimulating hormone. In particular, compound #2 remarkably lowered the mRNA and protein expression levels of microphthalmia-associated transcription factor (MITF), tyrosinase (TYR), tyrosinase-related protein 1 (TYRP1), and TYRP2 in B16F10 cells and substantially reduced skin pigmentation in the developed larvae of zebrafish. These findings suggest that compound #2 may be used as an anti-melanogenic agent for cosmetic purpose. Full article

(This article belongs to the Special Issue Melanins and Melanogenesis: From Nature to Applications)

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11 pages, 2996 KiB

Open AccessArticle

Antimelanogenic Effect of an Oroxylum indicum Seed Extract by Suppression of MITF Expression through Activation of MAPK Signaling Protein

by Peijun Zhao, Md Badrul Alam, Hongyan An, Hee-Jeong Choi, Yeong Ho Cha, Chi-Yeol Yoo, Hyo-Hyun Kim and Sang-Han Lee

Int. J. Mol. Sci. 2018, 19(3), 760; https://doi.org/10.3390/ijms19030760 - 7 Mar 2018

Cited by 10 | Viewed by 5220

Abstract

In this study, the antimelanogenic effect of an ethyl acetate fraction of Oroxylum indicum Vent. seeds (OISEA) and its underlying mechanisms in melan-a cells were investigated. Antimelanogenesis activity was confirmed by assessing inhibition of tyrosinase activity and melanin content in the cells. Both [...] Read more.

In this study, the antimelanogenic effect of an ethyl acetate fraction of Oroxylum indicum Vent. seeds (OISEA) and its underlying mechanisms in melan-a cells were investigated. Antimelanogenesis activity was confirmed by assessing inhibition of tyrosinase activity and melanin content in the cells. Both transcriptional and translational expression of microphthalmia-associated transcription factor (MITF), tyrosinase, and tyrosinase related protein-1 and 2 (TYRP-1 and TYRP-2), were also examined. The results depicted that pretreatment of OISEA significantly inhibits not only tyrosinase activity, but melanin production and intracellular tyrosinase activity. By repressing the expression of tyrosinase, TYRP-1, TYRP-2, and MITF, OISEA interrupted melanin production. Additionally, OISEA interfered with the phosphorylation of p38, extracellular signal-regulated kinase 1/2 (ERK1/2), and c-Jun N-terminal kinase (JNK), with the reversal of OISEA-induced melanogenesis inhibition after treatment with the specific inhibitors SB239063, U0126, and SP600125. Overall, these results suggest that OISEA can stimulate p38, ERK1/2, JNK phosphorylation, and subsequent suppression of melanin, leading to the inhibition of melanogenic enzymes and melanin production, possibly owing to the presence of polyphenolic compounds. Full article

(This article belongs to the Special Issue Melanins and Melanogenesis: From Nature to Applications)

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19 pages, 4229 KiB

Open AccessArticle

Novel Furocoumarin Derivatives Stimulate Melanogenesis in B16 Melanoma Cells by Up-Regulation of MITF and TYR Family via Akt/GSK3β/β-Catenin Signaling Pathways

by Chao Niu, Li Yin and Haji Akber Aisa

Int. J. Mol. Sci. 2018, 19(3), 746; https://doi.org/10.3390/ijms19030746 - 6 Mar 2018

Cited by 37 | Viewed by 6863

Abstract

The extracts of Ficuscarica L. and Psoralen corylifolia L. are traditional Uygur medicines for the treatment of vitiligo, and its active ingredients furocoumarins, were are found to be the most effective agents against this skin disorder nowadays. Therefore, a series of novel easter [...] Read more.

The extracts of Ficuscarica L. and Psoralen corylifolia L. are traditional Uygur medicines for the treatment of vitiligo, and its active ingredients furocoumarins, were are found to be the most effective agents against this skin disorder nowadays. Therefore, a series of novel easter derivatives (8a–8p) of furocoumarin were designed and synthesized based on our previous research to improve this activity in the present study. The synthesized derivatives were biologically evaluated for melanin synthesis in murine B16 cells and the SAR (structure-activity relationship) was summarized. Eight derivatives were more potent than positive control (8-MOP, 8-methoxypsoralan), especially compounds 8n (200%) and 8o (197%), which were nearly 1.5-fold potency when compared with 8-MOP (136%). Furthermore, the signaling pathway by which 8n activates the melanin biosynthesis was defined. Our results showed that it not only elevated the melanin content, but also stimulated the activity of tyrosinasein a concentration-dependent manner. Increasing of phosphorylation of Akt (also named PKB, protein kinase B) and non-activated GSK3β (glycogen synthase kinase 3 beta), which inhibited the degradation of β-catenin were observed through Western blot analysis. The accumulation of β-catenin probably led to the activation of transcription of MITF (microphthalmia-associated transcription factor) and TYR (tyrosinase) family, as well as the subsequent induction of melanin synthesis. Full article

(This article belongs to the Special Issue Melanins and Melanogenesis: From Nature to Applications)

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14 pages, 13463 KiB

Open AccessArticle

Structure-Activity Relationships of Thiazolyl Resorcinols, Potent and Selective Inhibitors of Human Tyrosinase

by Tobias Mann, Cathrin Scherner, Klaus-Heinrich Röhm and Ludger Kolbe

Int. J. Mol. Sci. 2018, 19(3), 690; https://doi.org/10.3390/ijms19030690 - 28 Feb 2018

Cited by 41 | Viewed by 9988

Abstract

Tyrosinase inhibitors are of great clinical interest as agents for the treatment of hyperpigmentary disorders; however, most compounds described in the literature lack clinical efficiency due to insufficient inhibitory activity against human tyrosinase (hTyr). Recently, we reported that thiazolyl resorcinols (4-resorcinylthiazol-2-amines and -amides) [...] Read more.

Tyrosinase inhibitors are of great clinical interest as agents for the treatment of hyperpigmentary disorders; however, most compounds described in the literature lack clinical efficiency due to insufficient inhibitory activity against human tyrosinase (hTyr). Recently, we reported that thiazolyl resorcinols (4-resorcinylthiazol-2-amines and -amides) are both selective and efficacious inhibitors of hTyr in vitro and in vivo. Here, we measured dose-activity profiles of a large number of thiazolyl resorcinols and analogous compounds to better understand the molecular basis of their interaction with hTyr. We show that both the resorcinyl moiety and the thiazole ring must be intact to allow efficient inhibition of hTyr, while the substituents at the thiazole 2-amino group confer additional inhibitory activity, depending on their size and polarity. The results of molecular docking simulations were in excellent agreement with the experimental data, affording a rationale for the structural importance of either ring. We further propose that a special type of interaction between the thiazole sulfur and a conserved asparagine residue is partially responsible for the superior inhibitory activity of thiazolyl resorcinols against hTyr. Full article

(This article belongs to the Special Issue Melanins and Melanogenesis: From Nature to Applications)

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14 pages, 1513 KiB

Open AccessArticle

Nanomechanical Phenotype of Melanoma Cells Depends Solely on the Amount of Endogenous Pigment in the Cells

by Michal Sarna, Andrzej Zadlo, Barbara Czuba-Pelech and Krystyna Urbanska

Int. J. Mol. Sci. 2018, 19(2), 607; https://doi.org/10.3390/ijms19020607 - 18 Feb 2018

Cited by 29 | Viewed by 4733

Abstract

Cancer cells have unique nanomechanical properties, i.e., they behave as if they were elastic. This property of cancer cells is believed to be one of the main reasons for their facilitated ability to spread and metastasize. Thus, the so-called nanomechanical phenotype of cancer [...] Read more.

Cancer cells have unique nanomechanical properties, i.e., they behave as if they were elastic. This property of cancer cells is believed to be one of the main reasons for their facilitated ability to spread and metastasize. Thus, the so-called nanomechanical phenotype of cancer cells is viewed as an important indicator of the cells’ metastatic behavior. One of the most highly metastatic cancer cells are melanoma cells, which have a very unusual property: they can synthesize the pigment melanin in large amounts, becoming heavily pigmented. So far, the role of melanin in melanoma remains unclear, particularly the impact of the pigment on metastatic behavior of melanoma cells. Importantly, until recently the potential mechanical role of melanin in melanoma metastasis was completely ignored. In this work, we examined melanoma cells isolated from hamster tumors containing endogenous melanin pigment. Applying an array of advanced microscopy and spectroscopy techniques, we determined that melanin is the dominating factor responsible for the mechanical properties of melanoma cells. Our results indicate that the nanomechanical phenotype of melanoma cells may be a reliable marker of the cells’ metastatic behavior and point to the important mechanical role of melanin in the process of metastasis of melanoma. Full article

(This article belongs to the Special Issue Melanins and Melanogenesis: From Nature to Applications)

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10 pages, 2181 KiB

Open AccessCommunication

AP-1/KIF13A Blocking Peptides Impair Melanosome Maturation and Melanin Synthesis

by Cécile Campagne, Léa Ripoll, Floriane Gilles-Marsens, Graça Raposo and Cédric Delevoye

Int. J. Mol. Sci. 2018, 19(2), 568; https://doi.org/10.3390/ijms19020568 - 14 Feb 2018

Cited by 11 | Viewed by 9026

Abstract

Melanocytes are specialized cells that generate unique organelles called melanosomes in which melanin is synthesized and stored. Melanosome biogenesis and melanocyte pigmentation require the transport and delivery of melanin synthesizing enzymes, such as tyrosinase and related proteins (e.g., TYRP1), from endosomes to maturing [...] Read more.

Melanocytes are specialized cells that generate unique organelles called melanosomes in which melanin is synthesized and stored. Melanosome biogenesis and melanocyte pigmentation require the transport and delivery of melanin synthesizing enzymes, such as tyrosinase and related proteins (e.g., TYRP1), from endosomes to maturing melanosomes. Among the proteins controlling endosome-melanosome transport, AP-1 together with KIF13A coordinates the endosomal sorting and trafficking of TYRP1 to melanosomes. We identify here β1-adaptin AP-1 subunit-derived peptides of 5 amino acids that block the interaction of KIF13A with AP-1 in cells. Incubating these peptides with human MNT-1 cells or 3D-reconstructed pigmented epidermis decreases pigmentation by impacting the maturation of melanosomes in fully pigmented organelles. This study highlights that peptides targeting the intracellular trafficking of melanocytes are candidate molecules to tune pigmentation in health and disease. Full article

(This article belongs to the Special Issue Melanins and Melanogenesis: From Nature to Applications)

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18 pages, 1649 KiB

Open AccessArticle

Antioxidative and Anti-Melanogenic Activities of Bamboo Stems (Phyllostachys nigra variety henosis) via PKA/CREB-Mediated MITF Downregulation in B16F10 Melanoma Cells

by Moon-Hee Choi, Han-Gyo Jo, Ji Hye Yang, Sung Hwan Ki and Hyun-Jae Shin

Int. J. Mol. Sci. 2018, 19(2), 409; https://doi.org/10.3390/ijms19020409 - 30 Jan 2018

Cited by 57 | Viewed by 8533

Abstract

Phyllostachys nigra var. henosis, a domestic bamboo species, has been attracting much attention; its bioactive compounds (especially in the leaf) show antioxidant, anti-inflammatory, and anti-obesity activities. Little information is available on the antioxidative and anti-melanogenetic activities of the bioactive compounds in bamboo stems. [...] Read more.

Phyllostachys nigra var. henosis, a domestic bamboo species, has been attracting much attention; its bioactive compounds (especially in the leaf) show antioxidant, anti-inflammatory, and anti-obesity activities. Little information is available on the antioxidative and anti-melanogenetic activities of the bioactive compounds in bamboo stems. The anti-melanogenic and antioxidative activities of the EtOAc fraction (PN3) of a P. nigra stem extract were investigated in a cell-free system and in B16F10 melanoma cells. PN3 consisted of a mixture of flavonoids, such as catechin, chlorogenic acid, caffeic acid, and p-coumaric acid. The antioxidant activity (2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS)), and hydroxyl radical scavenging) was evaluated, as well as the inhibition of reactive oxygen species (ROS) produced by the Fenton reaction. PN3 showed in vitro tyrosinase inhibition activity with the half maximal inbihitory concentration (IC₅₀) values of 240 μg/mL, and in vivo cytotoxic concentration ranges > 100 μg/mL. The protein expression levels and mRNA transcription levels of TYR, TRP-1, and MITF were decreased in a dose-dependent manner by the treatment with PN3. PN3 interfered with the phosphorylation of intracellular protein kinase A (PKA)/cAMP response element-binding protein (CREB), demonstrating potent anti-melanogenic effects. PN3 could inhibit PKA/CREB and the subsequent degradation of microphthalmia-associated transcription factor (MITF), resulting in the suppression of melanogenic enzymes and melanin production, probably because of the presence of flavonoid compounds. These properties make it a candidate as an additive to whitening cosmetics. Full article

(This article belongs to the Special Issue Melanins and Melanogenesis: From Nature to Applications)

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4551 KiB

Open AccessArticle

Selection on the Major Color Gene Melanocortin-1-Receptor Shaped the Evolution of the Melanocortin System Genes

by Linda Dib, Luis M. San-Jose, Anne-Lyse Ducrest, Nicolas Salamin and Alexandre Roulin

Int. J. Mol. Sci. 2017, 18(12), 2618; https://doi.org/10.3390/ijms18122618 - 5 Dec 2017

Cited by 22 | Viewed by 6676

Abstract

Modular genetic systems and networks have complex evolutionary histories shaped by selection acting on single genes as well as on their integrated function within the network. However, uncovering molecular coevolution requires the detection of coevolving sites in sequences. Detailed knowledge of the functions [...] Read more.

Modular genetic systems and networks have complex evolutionary histories shaped by selection acting on single genes as well as on their integrated function within the network. However, uncovering molecular coevolution requires the detection of coevolving sites in sequences. Detailed knowledge of the functions of each gene in the system is also necessary to identify the selective agents driving coevolution. Using recently developed computational tools, we investigated the effect of positive selection on the coevolution of ten major genes in the melanocortin system, responsible for multiple physiological functions and human diseases. Substitutions driven by positive selection at the melanocortin-1-receptor (MC1R) induced more coevolutionary changes on the system than positive selection on other genes in the system. Contrarily, selection on the highly pleiotropic POMC gene, which orchestrates the activation of the different melanocortin receptors, had the lowest coevolutionary influence. MC1R and possibly its main function, melanin pigmentation, seems to have influenced the evolution of the melanocortin system more than functions regulated by MC2-5Rs such as energy homeostasis, glucocorticoid-dependent stress and anti-inflammatory responses. Although replication in other regulatory systems is needed, this suggests that single functional aspects of a genetic network or system can be of higher importance than others in shaping coevolution among the genes that integrate it. Full article

(This article belongs to the Special Issue Melanins and Melanogenesis: From Nature to Applications)

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5454 KiB

Open AccessArticle

Effects of Extremely Low Frequency Electromagnetic Fields on Melanogenesis through p-ERK and p-SAPK/JNK Pathways in Human Melanocytes

by Yu-Mi Kim, Sang-Eun Cho, Soo-Chan Kim, Hyun-Joon Jang and Young-Kwon Seo

Int. J. Mol. Sci. 2017, 18(10), 2120; https://doi.org/10.3390/ijms18102120 - 11 Oct 2017

Cited by 15 | Viewed by 6590

Abstract

This study evaluated frequency-dependent effects of extremely low frequency electromagnetic fields (ELF-EMFs) on melanogenesis by melanocytes in vitro. Melanocytes were exposed to 2 mT EMFs at 30–75 Hz for 3 days before melanogenesis was examined. Exposure to ELF-EMFs at 50 and 60 Hz [...] Read more.

This study evaluated frequency-dependent effects of extremely low frequency electromagnetic fields (ELF-EMFs) on melanogenesis by melanocytes in vitro. Melanocytes were exposed to 2 mT EMFs at 30–75 Hz for 3 days before melanogenesis was examined. Exposure to ELF-EMFs at 50 and 60 Hz induced melanogenic maturation without cell damage, without changing cell proliferation and mitochondrial activity. Melanin content and tyrosinase activity of cells exposed to 50 Hz were higher than in controls, and mRNA expression of tyrosinase-related protein-2 was elevated relative to controls at 50 Hz. Phosphorylated cyclic adenosine monophosphate response element-binding protein (p-CREB) levels were higher than controls in cells exposed to ELF-EMFs at 50–75 Hz. Immunohistochemical staining showed that melanocyte-specific markers (HMB45, Melan-A) were strongly expressed in cells exposed to EMFs at 50 and 60 Hz compared to controls. Thus, exposure to ELF-EMFs at 50 Hz could stimulate melanogenesis in melanocytes, through activation of p-CREB and p-p38 and inhibition of phosphorylated extracellular signal-regulated protein kinase and phosphorylated stress-activated protein kinase/c-Jun N-terminal kinase. The results may form the basis of an appropriate anti-gray hair treatment or be applied in a therapeutic device for inducing repigmentation in the skin of vitiligo patients. Full article

(This article belongs to the Special Issue Melanins and Melanogenesis: From Nature to Applications)

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1942 KiB

Open AccessArticle

Inhibition of NAT10 Suppresses Melanogenesis and Melanoma Growth by Attenuating Microphthalmia-Associated Transcription Factor (MITF) Expression

by Taek-In Oh, Yoon-Mi Lee, Beong-Ou Lim and Ji-Hong Lim

Int. J. Mol. Sci. 2017, 18(9), 1924; https://doi.org/10.3390/ijms18091924 - 7 Sep 2017

Cited by 37 | Viewed by 8485

Abstract

N-acetyltransferase 10 (NAT10) has been considered a target for the treatment of human diseases such as cancer and laminopathies; however, its functional role in the biology of melanocytes is questionable. Using a small molecule or small interfering RNA targeting NAT10, we examined [...] Read more.

N-acetyltransferase 10 (NAT10) has been considered a target for the treatment of human diseases such as cancer and laminopathies; however, its functional role in the biology of melanocytes is questionable. Using a small molecule or small interfering RNA targeting NAT10, we examined the effect of NAT10 inhibition on melanogenesis and melanoma growth in human and mouse melanoma cells. Genetic silencing or chemical inhibition of NAT10 resulted in diminished melanin synthesis through the suppression of melanogenesis-stimulating genes such as those encoding dopachrome tautomerase (DCT) and tyrosinase in B16F10 melanoma cells. In addition, NAT10 inhibition significantly increased cell cycle arrest in S-phase, thereby suppressing the growth and proliferation of malignant melanoma cells in vitro and in vivo. These results demonstrate the potential role of NAT10 in melanogenesis and melanoma growth through the regulation of microphthalmia-associated transcription factor (MITF) expression and provide a promising strategy for the treatment of various skin diseases (melanoma) and pigmentation disorders (chloasma and freckles). Full article

(This article belongs to the Special Issue Melanins and Melanogenesis: From Nature to Applications)

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2020 KiB

Open AccessArticle

Protocatechuic Acid from Pear Inhibits Melanogenesis in Melanoma Cells

by Xuan T. Truong, Seo-Hee Park, Yu-Geon Lee, Hang Yeon Jeong, Jae-Hak Moon and Tae-Il Jeon

Int. J. Mol. Sci. 2017, 18(8), 1809; https://doi.org/10.3390/ijms18081809 - 21 Aug 2017

Cited by 37 | Viewed by 12151

Abstract

Despite the critical role of melanin in the protection of skin against UV radiation, excess production of melanin can lead to hyperpigmentation and skin cancer. Pear fruits are often used in traditional medicine for the treatment of melasma; therefore, we investigated the effects [...] Read more.

Despite the critical role of melanin in the protection of skin against UV radiation, excess production of melanin can lead to hyperpigmentation and skin cancer. Pear fruits are often used in traditional medicine for the treatment of melasma; therefore, we investigated the effects of pear extract (PE) and its component, protocatechuic acid (PCA), on melanogenesis in mouse melanoma cells. We found that PE and PCA significantly suppressed melanin content and cellular tyrosinase activity through a decrease in the expression of melanogenic enzymes and microphthalmia-associated transcription factor (Mitf) in α-melanocyte stimulating hormone-stimulated mouse melanoma cells. Moreover, PCA decreased cyclic adenosine monophosphate (cAMP) levels and cAMP-responsive element-binding protein phosphorylation, which downregulated Mitf promoter activation and subsequently mediated the inhibition of melanogenesis. These results suggested that pear may be an effective skin lightening agent that targets either a tyrosinase activity or a melanogenic pathway. Full article

(This article belongs to the Special Issue Melanins and Melanogenesis: From Nature to Applications)

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Review

Jump to: Editorial, Research

44 pages, 3421 KiB

Open AccessReview

Clinical and Biological Characterization of Skin Pigmentation Diversity and Its Consequences on UV Impact

by Sandra Del Bino, Christine Duval and Françoise Bernerd

Int. J. Mol. Sci. 2018, 19(9), 2668; https://doi.org/10.3390/ijms19092668 - 8 Sep 2018

Cited by 175 | Viewed by 25744

Abstract

Skin color diversity is the most variable and noticeable phenotypic trait in humans resulting from constitutive pigmentation variability. This paper will review the characterization of skin pigmentation diversity with a focus on the most recent data on the genetic basis of skin pigmentation, [...] Read more.

Skin color diversity is the most variable and noticeable phenotypic trait in humans resulting from constitutive pigmentation variability. This paper will review the characterization of skin pigmentation diversity with a focus on the most recent data on the genetic basis of skin pigmentation, and the various methodologies for skin color assessment. Then, melanocyte activity and amount, type and distribution of melanins, which are the main drivers for skin pigmentation, are described. Paracrine regulators of melanocyte microenvironment are also discussed. Skin response to sun exposure is also highly dependent on color diversity. Thus, sensitivity to solar wavelengths is examined in terms of acute effects such as sunburn/erythema or induced-pigmentation but also long-term consequences such as skin cancers, photoageing and pigmentary disorders. More pronounced sun-sensitivity in lighter or darker skin types depending on the detrimental effects and involved wavelengths is reviewed. Full article

(This article belongs to the Special Issue Melanins and Melanogenesis: From Nature to Applications)

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16 pages, 814 KiB

Open AccessReview

MC1R: Front and Center in the Bright Side of Dark Eumelanin and DNA Repair

by Viki B. Swope and Zalfa A. Abdel-Malek

Int. J. Mol. Sci. 2018, 19(9), 2667; https://doi.org/10.3390/ijms19092667 - 8 Sep 2018

Cited by 78 | Viewed by 11496

Abstract

Melanin, the pigment produced by specialized cells, melanocytes, is responsible for skin and hair color. Skin pigmentation is an important protective mechanism against the DNA damaging and mutagenic effects of solar ultraviolet radiation (UV). It is acknowledged that exposure to UV is the [...] Read more.

Melanin, the pigment produced by specialized cells, melanocytes, is responsible for skin and hair color. Skin pigmentation is an important protective mechanism against the DNA damaging and mutagenic effects of solar ultraviolet radiation (UV). It is acknowledged that exposure to UV is the main etiological environmental factor for all forms of skin cancer, including melanoma. DNA repair capacity is another major factor that determines the risk for skin cancer. Human melanocytes synthesize eumelanin, the dark brown form of melanin, as well as pheomelanin, which is reddish-yellow in color. The relative rates of eumelanin and pheomelanin synthesis by melanocytes determine skin color and the sensitivity of skin to the drastic effects of solar UV. Understanding the complex regulation of melanocyte function and how it responds to solar UV has a huge impact on developing novel photoprotective strategies to prevent skin cancer, particularly melanoma, the most fatal form, which originates from melanocytes. This review provides an overview of the known differences in the photoprotective effects of eumelanin versus pheomelanin, how these two forms of melanin are regulated genetically and biochemically, and their impact on the DNA damaging effects of UV exposure. Additionally, this review briefly discusses the role of paracrine factors, focusing on α-melanocortin (α-melanocyte stimulating hormone; α-MSH), in regulating melanogenesis and the response of melanocytes to UV, and describes a chemoprevention strategy based on targeting the melanocortin 1 receptor (MC1R) by analogs of its physiological agonist α-MSH. Full article

(This article belongs to the Special Issue Melanins and Melanogenesis: From Nature to Applications)

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16 pages, 1076 KiB

Open AccessReview

The Late Stages of Melanogenesis: Exploring the Chemical Facets and the Application Opportunities

by Lucia Panzella, Atsuko Ebato, Alessandra Napolitano and Kenzo Koike

Int. J. Mol. Sci. 2018, 19(6), 1753; https://doi.org/10.3390/ijms19061753 - 13 Jun 2018

Cited by 51 | Viewed by 7182

Abstract

In the last decade, the late stages of melanin biosynthesis involving the oxidative polymerization of 5,6-dihydroxyindole (DHI) and 5,6-dihydroxyindole-2-carboxylic acid (DHICA) have been extensively investigated. Most of the information derived from a biomimetic approach in which the oxidation of melanogenic indoles was carried [...] Read more.

In the last decade, the late stages of melanin biosynthesis involving the oxidative polymerization of 5,6-dihydroxyindole (DHI) and 5,6-dihydroxyindole-2-carboxylic acid (DHICA) have been extensively investigated. Most of the information derived from a biomimetic approach in which the oxidation of melanogenic indoles was carried out under conditions mimicking those occurring in the biological environment. Characterization of the early oligomers allowed for drawing a structural picture of DHI and DHICA melanins, providing also an interpretative basis for the different properties exhibited by these pigments, e.g., the chromophore and the antioxidant ability. The improved knowledge has opened new perspectives toward the exploitation of the unique chemistry of melanins and its precursors in cosmetic and health care applications. A noticeable example is the development of an innovative hair dyeing system that is based on the marked ease of DHI to give rise to black melanin on air oxidation under slightly alkaline conditions. The advantage of this method for a step-wise coverage of gray hair with a natural shade pigmentation on repeated treatment with a DHI-based formulation with respect to traditional dyes is presented. A variant of DHICA melanin combining solubility in water-miscible organic solvents, an intense chromophore in the UltraViolet-A UV-A region, and a marked antioxidant potency was evaluated as an ingredient for cosmetic formulations. Full article

(This article belongs to the Special Issue Melanins and Melanogenesis: From Nature to Applications)

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15 pages, 255 KiB

Open AccessReview

Clinical and Molecular Aspects of Vitiligo Treatments

by Anuradha Bishnoi and Davinder Parsad

Int. J. Mol. Sci. 2018, 19(5), 1509; https://doi.org/10.3390/ijms19051509 - 18 May 2018

Cited by 56 | Viewed by 9198

Abstract

Vitiligo is an asymptomatic but cosmetically disfiguring disorder that results in the formation of depigmented patches on skin and/or mucosae. Vitiligo can be segmental or non-segmental depending upon the morphology of the clinical involvement. It can also be classified as progressing or stable [...] Read more.

Vitiligo is an asymptomatic but cosmetically disfiguring disorder that results in the formation of depigmented patches on skin and/or mucosae. Vitiligo can be segmental or non-segmental depending upon the morphology of the clinical involvement. It can also be classified as progressing or stable based on the activity of the disease. Further, the extent of involvement can be limited (localized disease) or extensive (generalized disease). The treatment of vitiligo therefore depends on the clinical classification/characteristics of the disease and usually comprises of 2 strategies. The first involves arresting the progression of active disease (to provide stability) in order to limit the area involved by depigmentation. The second strategy aims at repigmentation of the depigmented area. It is also important to maintain the disease in a stable phase and to prevent relapse. Accordingly, a holistic treatment approach for vitiligo should be individualistic and should take care of all these considerations. In this review, we shall discuss the vitiligo treatments and their important clinical and molecular aspects. Full article

(This article belongs to the Special Issue Melanins and Melanogenesis: From Nature to Applications)

17 pages, 852 KiB

Open AccessReview

On the Metal Cofactor in the Tyrosinase Family

by Francisco Solano

Int. J. Mol. Sci. 2018, 19(2), 633; https://doi.org/10.3390/ijms19020633 - 23 Feb 2018

Cited by 81 | Viewed by 8123

Abstract

The production of pigment in mammalian melanocytes requires the contribution of at least three melanogenic enzymes, tyrosinase and two other accessory enzymes called the tyrosinase-related proteins (Trp1 and Trp2), which regulate the type and amount of melanin. The last two proteins are paralogues [...] Read more.

The production of pigment in mammalian melanocytes requires the contribution of at least three melanogenic enzymes, tyrosinase and two other accessory enzymes called the tyrosinase-related proteins (Trp1 and Trp2), which regulate the type and amount of melanin. The last two proteins are paralogues to tyrosinase, and they appeared late in evolution by triplication of the tyrosinase gene. Tyrosinase is a copper-enzyme, and Trp2 is a zinc-enzyme. Trp1 has been more elusive, and the direct identification of its metal cofactor has never been achieved. However, due to its enzymatic activity and similarities with tyrosinase, it has been assumed as a copper-enzyme. Recently, recombinant human tyrosinase and Trp1 have been expressed in enough amounts to achieve for the first time their crystallization. Unexpectedly, it has been found that Trp1 contains a couple of Zn(II) at the active site. This review discusses data about the metal cofactor of tyrosinase and Trps. It points out differences in the studied models, and it proposes some possible points accounting for the apparent discrepancies currently appearing. Moreover, some proposals about the possible flexibility of the tyrosinase family to uptake copper or zinc are discussed. Full article

(This article belongs to the Special Issue Melanins and Melanogenesis: From Nature to Applications)

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16 pages, 1389 KiB

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Biochemical Mechanism of Rhododendrol-Induced Leukoderma

by Shosuke Ito and Kazumasa Wakamatsu

Int. J. Mol. Sci. 2018, 19(2), 552; https://doi.org/10.3390/ijms19020552 - 12 Feb 2018

Cited by 31 | Viewed by 8803

Abstract

RS-4-(4-hydroxyphenyl)-2-butanol (rhododendrol (RD))—a skin-whitening ingredient—was reported to induce leukoderma in some consumers. We have examined the biochemical basis of the RD-induced leukoderma by elucidating the metabolic fate of RD in the course of tyrosinase-catalyzed oxidation. We found that the oxidation of racemic [...] Read more.

RS-4-(4-hydroxyphenyl)-2-butanol (rhododendrol (RD))—a skin-whitening ingredient—was reported to induce leukoderma in some consumers. We have examined the biochemical basis of the RD-induced leukoderma by elucidating the metabolic fate of RD in the course of tyrosinase-catalyzed oxidation. We found that the oxidation of racemic RD by mushroom tyrosinase rapidly produces RD-quinone, which gives rise to secondary quinone products. Subsequently, we confirmed that human tyrosinase is able to oxidize both enantiomers of RD. We then showed that B16 cells exposed to RD produce high levels of RD-pheomelanin and protein-SH adducts of RD-quinone. Our recent studies showed that RD-eumelanin—an oxidation product of RD—exhibits a potent pro-oxidant activity that is enhanced by ultraviolet-A radiation. In this review, we summarize our biochemical findings on the tyrosinase-dependent metabolism of RD and related studies by other research groups. The results suggest two major mechanisms of cytotoxicity to melanocytes. One is the cytotoxicity of RD-quinone through binding with sulfhydryl proteins that leads to the inactivation of sulfhydryl enzymes and protein denaturation that leads to endoplasmic reticulum stress. The other mechanism is the pro-oxidant activity of RD-derived melanins that leads to oxidative stress resulting from the depletion of antioxidants and the generation of reactive oxygen radicals. Full article

(This article belongs to the Special Issue Melanins and Melanogenesis: From Nature to Applications)

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11 pages, 2214 KiB

Open AccessReview

Melanins in Fossil Animals: Is It Possible to Infer Life History Traits from the Coloration of Extinct Species?

by Juan J. Negro, Clive Finlayson and Ismael Galván

Int. J. Mol. Sci. 2018, 19(2), 230; https://doi.org/10.3390/ijms19020230 - 23 Jan 2018

Cited by 14 | Viewed by 8891

Abstract

Paleo-colour scientists have recently made the transition from describing melanin-based colouration in fossil specimens to inferring life-history traits of the species involved. Two such cases correspond to counter-shaded dinosaurs: dark-coloured due to melanins dorsally, and light-coloured ventrally. We believe that colour reconstruction of [...] Read more.

Paleo-colour scientists have recently made the transition from describing melanin-based colouration in fossil specimens to inferring life-history traits of the species involved. Two such cases correspond to counter-shaded dinosaurs: dark-coloured due to melanins dorsally, and light-coloured ventrally. We believe that colour reconstruction of fossils based on the shape of preserved microstructures—the majority of paleo-colour studies involve melanin granules—is not without risks. In addition, animals with contrasting dorso-ventral colouration may be under different selection pressures beyond the need for camouflage, including, for instance, visual communication or ultraviolet (UV) protection. Melanin production is costly, and animals may invest less in areas of the integument where pigments are less needed. In addition, melanocytes exposed to UV radiation produce more melanin than unexposed melanocytes. Pigment economization may thus explain the colour pattern of some counter-shaded animals, including extinct species. Even in well-studied extant species, their diversity of hues and patterns is far from being understood; inferring colours and their functions in species only known from one or few specimens from the fossil record should be exerted with special prudence. Full article

(This article belongs to the Special Issue Melanins and Melanogenesis: From Nature to Applications)

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8339 KiB

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Neural Stem Cells and Its Derivatives as a New Material for Melanin Inhibition

by Insik Hwang and Sunghoi Hong

Int. J. Mol. Sci. 2018, 19(1), 36; https://doi.org/10.3390/ijms19010036 - 22 Dec 2017

Cited by 12 | Viewed by 6003

Abstract

The pigment molecule, melanin, is produced from melanosomes of melanocytes through melanogenesis, which is a complex process involving a combination of chemical and enzymatically catalyzed reactions. The synthesis of melanin is primarily influenced by tyrosinase (TYR), which has attracted interest as a target [...] Read more.

The pigment molecule, melanin, is produced from melanosomes of melanocytes through melanogenesis, which is a complex process involving a combination of chemical and enzymatically catalyzed reactions. The synthesis of melanin is primarily influenced by tyrosinase (TYR), which has attracted interest as a target molecule for the regulation of pigmentation or depigmentation in skin. Thus, direct inhibitors of TYR activity have been sought from various natural and synthetic materials. However, due to issues with these inhibitors, such as weak or permanent ability for depigmentation, allergy, irritant dermatitis and rapid oxidation, in vitro and in vivo, the development of new materials that inhibit melanin production is essential. A conditioned medium (CM) derived from stem cells contains many cell-secreted factors, such as cytokines, chemokines, growth factors and extracellular vesicles including exosomes. In addition, the secreted factors could negatively regulate melanin production through stimulation of a microenvironment of skin tissue in a paracrine manner, which allows the neural stem cell CM to be explored as a new material for skin depigmentation. In this review, we will summarize the current knowledge regulating depigmentation, and discuss the potential of neural stem cells and their derivatives, as a new material for skin depigmentation. Full article

(This article belongs to the Special Issue Melanins and Melanogenesis: From Nature to Applications)

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