Skin Melanogenesis Research Articles

Wnt5a negatively regulates melanogenesis in primary Arctic fox epidermal melanocytes

Melanocytes, which are mainly found in the epidermis, are responsible for the melanin of skin and hair, and thereby contribute to the appearance of skin and provide protection from damage by ultraviolet radiation. Our previous study revealed that the Wnt5a, one of the many genes that affect melanin production, might be involved in the coat color seasonal change of the Arctic fox by influencing skin melanogenesis. Although the role of Wnt5a in melanocyte lines and melanoma cells has been extensively studied, its role in primary epidermal melanocytes has not been explored. This study aimed to investigate the role and mechanism of the Wnt5a in influencing melanogenesis in Arctic fox primary epidermal melanocytes. We constructed the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) knockout plasmid targeting exons of the Wnt5a and transfected it into primary epidermal melanocytes. The results of the amplification knockout region assay, RT-qPCR assay, and western blot assay showed the success of Wnt5a knockout. RT-qPCR assay and melanin content assay showed that melanin production in melanocytes was significantly increased after Wnt5a knockout, and melanin-related key genes, such as microphthalmia-associated transcription factor, tyrosinase and tyrosinase-related protein 1, were significantly elevated. In addition, we also found that the expression of the β-catenin gene of the Wnt canonical pathway was significantly elevated after Wnt5a knockout. In conclusion, our results indicate that the Wnt5a plays a negative regulatory role in melanogenesis in primary epidermal melanocytes, and is presumably involved in antagonizing or inhibiting canonical Wnt signaling.

A gain-of-function variant in SREBF1 causes generalized skin hyperpigmentation with congenital cataracts.

Lipid metabolism has essential roles in skin barrier formation and the regulation of skin inflammation. Lipid homeostasis regulates skin melanogenesis, although the underlying mechanism remains largely unknown. Sterol regulatory element binding protein 1 (SREBP-1) is a key transcription factor essential for cellular lipid metabolism. Loss-of-function variants in SREBF1 are responsible for autosomal-dominant ichthyosis follicularis, alopecia and photophobia syndrome, emphasizing the significance of lipid homeostasis in skin keratinization. To identify the genetic basis of a new entity featuring diffuse skin hyperpigmentation with congenital cataracts, and to unravel the underlying mechanism for the pathogenesis of the SREBF1 variant. Whole-exome sequencing was performed to identify underlying genetic variants. Quantitative polymerase chain reaction, Western blot and immunofluorescence staining were used to assess the expression and the subcellular localization of the SREBF1 variant. The transcriptional activity of mutant SREBP-1 was determined by a luciferase reporter assay. A transgenic zebrafish model was constructed. Two unrelated patients presented with generalized skin hyperpigmentation with skin xerosis, congenital cataracts and extracutaneous symptoms. We identified a de novo nonsense variant c.1289C>A (p.Ser430*) in SREBF1 in both patients. The variant encoded a truncated protein that showed preferential nucleus localization, in contrast to wild-type SREBP-1 which - in sterol-sufficient conditions - is mainly localized in the cytoplasm. The luciferase reporter assay revealed that the p.Ser430* mutant exhibited enhanced transcriptional activity. Cultured patient primary melanocytes showed increased melanin synthesis vs. those from healthy controls. At 35 days postfertilization, the p.Ser430* transgenic zebrafish model exhibited more black spots, along with upregulated expression of melanogenic genes. We demonstrated that a gain-of-function variant of SREBF1 causes a previously undescribed disorder characterized by generalized skin hyperpigmentation and congenital cataracts. Our study reveals the involvement of SREBP-1 in melanogenesis and lens development, and paves the way for the development of novel therapeutic targets for skin dyspigmentation or cataracts.

Loss-of-function variants in GLMN are associated with generalized skin hyperpigmentation with or without glomuvenous malformation.

Inherited hyperpigmented skin disorders comprise a group of entities with considerable clinical and genetic heterogenicity. The genetic basis of a majority of these disorders remains to be elucidated. This study aimed to identify the underlying gene for an unclarified disorder of autosomal-dominant generalized skin hyperpigmentation with or without glomuvenous malformation. Whole-exome sequencing was performed in five unrelated families with autosomal-dominant generalized skin hyperpigmentation. Variants were confirmed using Sanger sequencing and a minigene assay was employed to evaluate the splicing alteration. Immunofluorescence and transmission electron microscopy (TEM) were used to determine the quantity of melanocytes and melanosomes in hyperpigmented skin lesions. GLMN knockdown by small interfering RNA assays was performed in human MNT-1 cells to examine melanin concentration and the underlying molecular mechanism. We identified five variants in GLMN in five unrelated families, including c.995_996insAACA(p.Ser333Thrfs*11), c.632 + 4delA, c.1470_1473dup(p.Thr492fs*12), c.1319G > A(p.Trp440*) and c.1613_1614insTA(Thr540*). The minigene assay confirmed that the c.632 + 4delA mutant resulted in abolishment of the canonical donor splice site. Although the number of melanocytes remained unchanged in skin lesions, as demonstrated by immunofluorescent staining of tyrosinase and premelanosome protein, TEM revealed an increased number of melanosomes in the skin lesion of a patient. The GLMN knockdown MNT-1 cells demonstrated a higher melanin concentration, a higher proportion of stage III and IV melanosomes, upregulation of microphthalmia-associated transcription factor and tyrosinase, and downregulation of phosphorylated p70S6 K vs. mock-transfected cells. We found that loss-of-function variants in GLMN are associated with generalized skin hyperpigmentation with or without glomuvenous malformation. Our study implicates a potential role of glomulin in human skin melanogenesis, in addition to vascular morphogenesis.

Anti-melanin and tyrosinase inhibition mechanism of polydatin and 6″-O-lauryl polydatin synthesized by microwave-assisted enzymatic catalysis

Exploiting efficient tyrosinase inhibitors and utilizing the inhibition mechanism are of great significance to avoid enzymatic browning in food and skin melanogenesis. Polydatin had excellent tyrosinase inhibitory activity in vitro with IC50 value of 24.90 μM; however, it exhibited unsatisfactory inhibitory activity intracellularly, which was associated with poor cellular uptake. Fortunately, 6″-O-lauryl polydatin was green-efficiently synthesized by lipase-catalyzed acylation under microwave irradiation. 6″-O-lauryl polydatin exhibited superior mono-/diphenolase inhibitory activity within 100 μM than kojic acid, which had IC50 of 221 μM. Neither polydatin nor 6″-O-lauryl polydatin bound to the catalytic site, but rather bound noncovalently to the allosteric site 2 of tyrosinase through hydrogen bonds and hydrophobic interactions according to molecular simulations, thereby inducing secondary structure unfolding and reducing tyrosinase activity. 6″-O-lauryl polydatin showed stronger anti-browning effects than polydatin in the natural storage of potato and apple pieces. Polydatin and kojic acid did not induce apoptosis, but 6″-O-lauryl polydatin inhibited human melanin A375 cell proliferation by stimulating ROS overproduction and regulating cell cycle and apoptotic pathways. In addition, lipophilic 6″-O-lauryl polydatin had greater cellular uptake though suffered from intracellular hydrolysis, and exerted better tyrosinase and melanogenesis inhibitory activity than polydatin and kojic acid based on mouse B16F10 melanoma cell model. The results suggested polydatin and 6″-O-lauryl polydatin were promising tyrosinase inhibitors for anti-browning in foods or cosmetics fields.

Putrescine Upregulates Melanogenesis Through Modulation of MITF Transcription Factor in B16F1 Mouse Melanoma Cells.

Ageing is a biochemical, metabolic and genetic physiological phenomenon. The suppression of melanin biosynthesis, evident in the greying of the hair, is a hallmark of ageing resulting from translation failure, reduced enzyme activity and cellular senescence. Putrescine, the smallest member of the polyamine family and an organic chemical, is present in living mammalian cells and plays a crucial role in regulating skin melanogenesis. Therefore, the purpose of this study is to explore the effect of putrescine on the signalling pathways of melanogenesis in melanoma cells. Melanin production capacity of putrescine was analysed using a tyrosinase activity assay. To assess the cell viability of B16F1 cells exposed to putrescine, a tetrazolium dye MTT assay was performed. The effect of putrescine on melanin synthesis in the presence of H2O2 was evaluated using various in vitro assays in B16F1 cells. The effect of putrescine on melanin production in B16F1 cells was determined using a specific melanin production assay. Gene expression was analysed using real-time polymerase chain reaction (RT-PCR). Furthermore, the effect of putrescine on the expression of proteins related to melanin production in the cells treated with H2O2 was analysed by immunofluorescence and Western blot analysis. Putrescine increased tyrosinase activity and showed no cytotoxicity in B16F1 cells. In addition, putrescine effectively scavenged H2O2, as shown by the reduction of intracellular H2O2 amounts in 2',7'-dichlorofluorescin diacetate analysis, and promoted melanin production in living cells. The stimulation of melanogenesis by putrescine was attributed to the increased expression of Mitf, Tyr, Trp-1 and Trp-2 genes. Immunofluorescence assays revealed that putrescine enhanced the expression of proteins associated with melanogenesis and upregulated TYR, TRP-1 and TRP-2 via the microphthalmia-associated transcription factor (MITF) and increased the expression of methionine sulfoxide reductases A (MSRA) and B (MSRB) in the cells treated with H2O2, effectively promoting melanogenesis. These results suggest that putrescine can be used to stimulate melanin synthesis. This is the first study to investigate the effect of putrescine on the signalling pathways of melanogenesis in B16F1 melanoma cells. The results confirm that putrescine can promote melanogenesis through the expression of TYR, TRP-1 and TRP-2 via the MITF in cells treated with H2O2. Putrescine can be used exclusively as a cosmetic product to prevent premature greying of hair.

Heat promotes melanogenesis by increasing the paracrine effects in keratinocytes via the TRPV3/Ca2+/Hh signaling pathway

Global warming and rising temperature significantly increase the incidence of heat stress, which is known to affect the process of inflammation and aging. However, the effect of heat stress on skin melanogenesis is not fully known. We found that healthy foreskin tissues underwent significant pigmentation when exposed to 41°C. Furthermore, heat stress promoted melanogenesis in pigment cells by increasing the paracrine effects of keratinocytes. High-throughput RNA sequencing showed that heat stress activates the Hedgehog (Hh) signaling pathway in keratinocytes. The agonists of Hh signaling promote the paracrine effect of keratinocytes on melanogenesis. In addition, transient receptor potential vanilloid (TRPV) 3 agonists activate the Hh signaling in keratinocytes and augment its paracrine effect on melanogenesis. The heat-induced activation of Hh signaling is dependent on TRPV3-mediated Ca2+ influx. Heat exposure promotes melanogenesis by increasing the paracrine effects in keratinocytes via the TRPV3/Ca2+/Hh signaling pathway. Our findings provide insights into the mechanisms of heat-induced skin pigmentation.

Integrated analysis of long non-coding RNAs and mRNA expression profiles identified potential interactions regulating melanogenesis in chicken skin

ABSTRACT 1. Long non-coding RNAs (lncRNAs) play important roles in various physiological functions. However, the mechanisms underlying the regulation of lncRNAs in melanogenesis remain unclear. To determine the molecular mechanisms involved in skin melanogenesis, the present study depicted the expression profiles of lncRNAs and messenger RNAs (mRNAs) in black- (B group) and white- (W group) skinned chickens using RNA sequencing. 2. In total, 373 differentially expressed lncRNAs (DELs; 203 up-regulated and 170 down-regulated) and 253 differentially expressed genes (DEGs; 152 up-regulated and 101 down-regulated) were identified between the B and W groups. A total of eight known melanogenesis-related genes were identified (KIT, TYRP1, DCT (TYRP2), SLC45A2, OCA2, EDNRB2, TRPM1 and RAB38). 3. Functional annotation of the co-expressed DEGs and DELs was performed using Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analyses. The co-expressed DEGs were mainly involved in melanogenesis and the co-expressed genes of 117 and 108 DELs were significantly enriched in the melanogenesis and tyrosine metabolism pathways, respectively. 4. The DEL-DEG interaction network revealed that three lncRNAs (XR_003072387.1, XR_003075112.1, and XR_003077033.1) and DCT genes may have key roles in regulating melanogenesis in chicken skin. This data provides the groundwork for studying the lncRNA regulatory mechanisms of skin melanogenesis and suggested a new perspective on the modulation of melanogenesis in chicken skin based on a lncRNA-mRNA causal regulatory network.

Particulate matter 2.5 induced hyperpigmentation in reconstructed human epidermis model (MelaKutis®).

Particulate matter 2.5 induced hyperpigmentation in reconstructed human epidermis model (MelaKutis®).

Protective Effects of Polyvinylpyrrolidone-Wrapped Fullerene Against Nitric Oxide/Peroxynitrite-Induced Cellular Injury in Human Skin Keratinocytes.

Excess ultraviolet (UV) exposure accelerates skin inflammation, melanogenesis, wrinkle formation, photoaging, and carcinogenesis through oxidative stress and deoxyribonucleic acid damage. These deleterious effects to skin are closely associated with UV-induced reactive oxygen species (ROS) and reactive nitrogen species (RNS) produced via nitric oxide (NO·) generation. RNS are known to be responsible for various skin disorders, such as erythema, melanin production, reduced barrier function, and psoriasis. These skin disorders are major cosmetic problems; RNS control, in addition to ROS control, is important for maintaining healthy skin. In the present study, we investigated the cytoprotective effects of polyvinylpyrrolidone-entrapped fullerene (C60/PVP), a water-soluble ROS scavenger, against nitric oxide (NO·) and peroxynitrite (ONOO-)-induced human keratinocyte injuries. Protective effects of C60/PVP on NO·/ONOO--induced cellular damage and intracellular ONOO- generation were evaluated using a NO· donor S-nitroso-N-acetylpenicillamine (SNAP) in human skin epidermal HaCaT keratinocytes. Furthermore, the suppressive effect of C60/PVP on UVB-induced generation of intracellular ONOO- levels was also investigated. C60/PVP exerted suppressive effects on intracellular increases in NO·-induced ONOO- generation and subsequent cellular damage. Additionally, C60/PVP significantly decreased the UVB-induced generation of intracellular ONOO- levels. These findings suggest that C60/PVP could be useful as a cosmetics ingredient for prevention of skin injuries and/or dysfunction from NO·/ONOO--induced effects in human skin keratinocytes.

Oxidative stress in the skin: Impact and related protection.

Skin, our first interface to the external environment, is subjected to oxidative stress caused by a variety of factors such as solar ultraviolet, infrared and visible light, environmental pollution, including ozone and particulate matters, and psychological stress. Excessive reactive species, including reactive oxygen species and reactive nitrogen species, exacerbate skin pigmentation and aging, which further lead to skin tone unevenness, pigmentary disorder, skin roughness and wrinkles. Besides these, skin microbiota are also a very important factor ensuring the proper functions of skin. While environmental factors such as UV and pollutants impact skin microbiota compositions, skin dysbiosis results in various skin conditions. In this review, we summarize the generation of oxidative stress from exogenous and endogenous sources. We further introduce current knowledge on the possible roles of oxidative stress in skin pigmentation and aging, specifically with emphasis on oxidative stress and skin pigmentation. Meanwhile, we summarize the science and rationale of using three well-known antioxidants, namely vitamin C, resveratrol and ferulic acid, in the treatment of hyperpigmentation. Finally, we discuss the strategy for preventing oxidative stress-induced skin pigmentation and aging.

Capsaicin Inhibits the Expression of Melanogenic Proteins in Melanocyte via Activation of TRPV1 Channel: Identifying an Inhibitor of Skin Melanogenesis.

Chili pepper belongs to the genus Capsicum of Solanaceae family. Capsaicin is the primary capsaicinoid in placenta and flesh of chili pepper fruit, which has been shown to have various pharmacological functions, including gastric protection, anti-inflammation, and obesity treatment. Here, we revealed that capsaicin as well as chilli extract was able to inhibit synthesis of melanin in melanocytes. In cultured melanocytes, the melanin content was reduced to 54 ± 6.55% and 42 ± 7.41% with p < 0.001 under treatment of 50 μM capsaicin for 24 and 72 h, respectively. In parallel, the protein levels of tyrosinase and tyrosinase-related protein-1 were reduced to 62 ± 8.35% and 48 ± 8.92% with p < 0.001. Such an inhibitory effect of capsaicin was mediated by activation of transient receptor potential vanilloid 1-induced phosphorylation of extracellular signal-regulated kinase. This resulted in a degradation of microphthalmia-associated transcription factor, leading to reduction of melanogenic enzymes and melanin. These results revealed that capsaicin could be an effective inhibitor for skin melanogenesis. Hence, chili pepper, as our daily food, has potential in dermatological application, and capsaicin should be considered as a safe agent in treating hyperpigmentation problems.

&lt;i&gt;Nelumbo nucifera&lt;/i&gt; Leaf Extracts Inhibit Melanogenesis in B16 Melanoma Cells and Guinea Pigs through Downregulation of CREB/MITF Activation

Nelumbo nucifera leaves extracts (NLE) has been suggested to provide antioxidant, anti-obesity and anticancer effects. However, the research on the anti-melanogenetic effect of NLE was little. Here, we reported that NLE and Gallic acid (GA, major ingredients of NLE) exhibit the hypopigmentary effect in B16F1 cells. NLE and GA showed potent inhibitory effects on tyrosinase, microphthalmia-associated transcription factor (MITF), and tyrosinase-related protein-1 (TRP-1) protein production. The phosphorylation of intracellular protein kinase A (PKA) and cAMP response element-binding protein (CREB) were also decreased, revealing potent anti-melanogenic effects of NLE and GA. However, NLE showed the better effect than GA on reducing melanin formation, implying the importance of the synergism of polyphenolic compounds of NLE. Furthermore, NLE inhibited skin melanogenesis and epidermal hyperplasia of guinea pigs caused by irradiation through attenuating ERK and CREB activation. NLE reduced skin melanogenesis and epidermal hyperplasia induced by UVB in guinea pigs through downregulation ERK and CREB pathways, and the following decreasing of MITF, tyrosinase and TRP-1 expression. These results demonstrated the potential which NLE as an ingredient of hypopigmentary cosmetics.

Identifying and profiling the microRNAs associated with skin colour in the Muchuan black-bone chicken

MicroRNAs (miRNAs) are an abundant class of small non-protein-coding RNAs that regulate gene expression in plants and animals. Skin colour is an important economic consideration in chicken production, and chickens with black skin have high market value. Nevertheless, little research has been conducted on miRNA regulation of melanogenesis in chicken skin. In this study, we sampled the dorsal skins of chickens with black (BS) and white (WS) skin to construct six small RNA libraries. High-throughput sequencing technology was then used to identify which miRNAs were expressed differentially between the BS and WS phenotypes. A total of 645 known and 64 novel miRNAs were identified from the six sequencing libraries. Additionally, the expression of 18 miRNAs was significantly different between the two phenotypes, including 9 miRNAs that were up-regulated, and 9 that were down-regulated. We identified 2 miRNAs, i.e. miR-204 and miR-6631-5p, that may be important for melanogenesis in chicken skin. Our data contribute to the understanding of the molecular mechanism, through miRNA regulation, of melanin formation in chicken skin. Highlights Differentially expressed miRNAs were identified in black skin (BS) and white skin (WS) of black-bone chickens Eighteen DEMs were detected in BS and WS groups. miR-204 and miR-6631-5p were potential candidates influencing skin melanogenesis in chicken.

Flumequine-Mediated Upregulation of p38 MAPK and JNK Results in Melanogenesis in B16F10 Cells and Zebrafish Larvae.

Flumequine is a well-known second generation quinolone antibiotic that induces phototoxicity. However, the effect of flumequine on skin melanogenesis is unclear. Therefore, we, for the first time, investigated whether flumequine regulates melanogenesis. The present study showed that flumequine slightly inhibited in vitro mushroom tyrosinase activity but significantly increased extracellular and intracellular melanin content in B16F10 cells and promoted the expression of microphthalmia-associated transcription factor (MITF) and tyrosinase. Additionally, flumequine remarkably increased melanin pigmentation in zebrafish larvae without any toxicity. We also found that flumequine stimulated p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) phosphorylation; inhibition of p38 MAPK and JNK resulted in significant downregulation of extracellular and intracellular melanin content in B16F10 cells and pigmentation of zebrafish larvae accompanied with suppression of MITF and tyrosinase expression, indicating that flumequine-mediated p38 and JNK promote melanogenesis in vitro and in vivo. According to the molecular docking prediction, flumequine targeted dual-specificity MAPK phosphatase 16 (DUSP16), which is a major negative regulator of p38 MAPK and JNK. Our findings demonstrate that flumequine induces an increase in melanin content in B16F10 cells and zebrafish larvae by activating p38 MAPK and JNK. These data show the potential of flumequine for use as an anti-vitiligo agent.

Five alternative splicing variants of the TYR gene and their different roles in melanogenesis in the Muchuan black-boned chicken

ABSTRACT1. The TYR gene encodes tyrosinase, a multifunctional enzyme that is essential for melanin biosynthesis in melanocytes. This experiment involved the cloning and characterisation of the TYR gene in chicken. Five alternative splice variants were identified in the black feather bulb and designated as TYR-AS1, TYR-AS2, TYR-AS3, TYR-AS4 and TYR-AS5.2. Among the 11 chicken tissues examined, the feather bulb, comb and skin showed higher levels of all TYR variants. All TYR variants were expressed at significantly different levels in black and white feather bulbs (P < 0.05) and may be involved in melanin formation in plumage. Only TYR-AS1, which plays an important role in muscle melanogenesis, was significantly differentially expressed between black and white muscle (P < 0.01). All TYR variants were expressed at significantly different levels in black and white skin (P < 0.01).3. The mRNA expression levels of the 5 variants were closely associated with skin melanogenesis in the chicken. These findings provide new clues to the molecular mechanism of melanin formation in the Muchuan black-boned chicken.

Intrinsic and extrinsic regulation of human skin melanogenesis and pigmentation.

In human skin, melanogenesis is a tightly regulated process. Indeed, several extracellular signals are transduced via dedicated signalling pathways and mostly converge to MITF, a transcription factor integrating upstream signalling and regulating downstream genes involved in the various inherent mechanisms modulating melanogenesis. The synthesis of melanin pigments occurs in melanocytes inside melanosomes where melanogenic enzymes (tyrosinase and related proteins) are addressed with the help of specific protein complexes. The melanosomes loaded with melanin are then transferred to keratinocytes. A more elaborate level of melanogenesis regulation comes into play via the action of non-coding RNAs (microRNAs, lncRNAs). Besides this canonical regulation, melanogenesis can also be modulated by other non-specific intrinsic pathways (hormonal environment, inflammation) and by extrinsic factors (solar irradiation such as ultraviolet irradiation, environmental pollution). We developed a bioinformatic interaction network gathering the multiple aspects of melanogenesis and skin pigmentation as a resource to better understand and study skin pigmentation biology.

IDH2 deficiency accelerates skin pigmentation in mice via enhancing melanogenesis

Melanogenesis is a complex biosynthetic pathway regulated by multiple agents, which are involved in the production, transport, and release of melanin. Melanin has diverse roles, including determination of visible skin color and photoprotection. Studies indicate that melanin synthesis is tightly linked to the interaction between melanocytes and keratinocytes. α-melanocyte-stimulating hormone (α-MSH) is known as a trigger that enhances melanin biosynthesis in melanocytes through paracrine effects. Accumulated reactive oxygen species (ROS) in skin affects both keratinocytes and melanocytes by causing DNA damage, which eventually leads to the stimulation of α-MSH production. Mitochondria are one of the main sources of ROS in the skin and play a central role in modulating redox-dependent cellular processes such as metabolism and apoptosis. Therefore, mitochondrial dysfunction may serve as a key for the pathogenesis of skin melanogenesis. Mitochondrial NADP+-dependent isocitrate dehydrogenase (IDH2) is a key enzyme that regulates mitochondrial redox balance and reduces oxidative stress-induced cell injury through the generation of NADPH. Downregulation of IDH2 expression resulted in an increase in oxidative DNA damage in mice skin through ROS-dependent ATM-mediated p53 signaling. IDH2 deficiency also promoted pigmentation on the dorsal skin of mice, as evident from the elevated levels of melanin synthesis markers. Furthermore, pretreatment with mitochondria-targeted antioxidant mito-TEMPO alleviated oxidative DNA damage and melanogenesis induced by IDH2 deficiency both in vitro and in vivo. Together, our findings highlight the role of IDH2 in skin melanogenesis in association with mitochondrial ROS and suggest unique therapeutic strategies for the prevention of skin pigmentation.

Effects of dietary cystine and tyrosine on melanogenesis pathways involved in skin color differentiation of Malaysian red tilapia

A 68-day experiment was conducted to investigate the effects of dietary cystine (Cys) and tyrosine (Tyr) on skin melanogenesis pathways in Malaysian red tilapia (initial weight: 15.04 ± 0.03 g). Six practical diets containing extra 0.1%, 0.5%, 1% cystine (Cys) and 0.5%, 1%, 2% tyrosine (Tyr) based on the control diet were prepared, accordingly named as Control, Cys-0.1%, Cys-0.5%, Cys-1%, Tyr-0.5%, Tyr-1% and Tyr-2% respectively. Each diet was fed to triplicate groups of fish during the trial. At the end of the experiment, the final weight for each group was not significantly different (P > 0.05). However, the dietary Cys and Tyr had significant effects on the melanin level and tyrosinase activity in the skin of fish. The melanin content in the skin of fish was lowest in Cys-0.5% group, with a higher level observed at Cys-0.1% and Cys-1% group. The final melanin of fish skin in Cys-1% was higher than that in Cys-0.5% and Cys-0.1% (P < 0.05). At the end of the experiment, the melanin in ventral skin of fish in Tyr-2% was higher than that in Tyr-0.5% and Tyr-1% (P < 0.05), and the melanin in dorsal skin of fish in Tyr-0.5% was lower than that in Tyr-1% and Tyr-2% (P < 0.05). The final tyrosinase activity of fish skin in Cys-1% was highest, and the final tyrosinase activity in Tyr-1% and Tyr-2% were significantly higher than that in Tyr-0.5% (P < 0.05). In serum, the tyrosinase activity was highest in Cys-1%, and the tyrosinase activity in Tyr-2% was significantly higher than that in Tyr-1% and Tyr-0.5% (P < 0.05). Moreover, the ventral skin melanin zone in Cys-1% treatment is largest by slice microstructure observation. The expression of tyrosinase mRNA in Tyr-2% group was highest in ventral skin of fish. At the end of the experiment, tyrosinase mRNA in the dorsal skin of fish was lowest in Cys-0.5%, with a higher level observed at Cys-0.1% and Cys-1% group. The final expression of tyrosinase mRNA in Tyr-0.5% was lower than that in Tyr-1% and Tyr-2% in dorsal skin of fish (P < 0.05). The final expressions of slc7a11 mRNA in Tyr-1% was higher than that in Tyr-0.5% in dorsal skin of fish (P < 0.05). Present results demonstrated that dietary Cys and Tyr could affect the melanin synthesis pathway in the red tilapia.

Illumina-sequencing based transcriptome study of coat color phenotypes in domestic goats

This study performed a comprehensive expression profiling of genes expressed in the skin of goats with three different coat colors by Illumina Sequencing. A total of 91 significantly expressed genes were detected when comparing gray skin to white skin library and these included 74 up-regulated and 17 down-regulated genes in gray skin. There were 67 differentially expressed genes between brown skin and white skin libraries, 23 of which were up-regulated and 44 were down-regulated in brown skin. When we compared brown and gray libraries, 154 differentially expressed genes were found, of which 33 showed higher expression and 121 showed lower expression in brown skin. To our surprise, MC1R, MITF, TYR and KIT showed no significant difference in expression between the goats with three skin colors, whereas ASIP was detected in white skin but not in dark skins. In this study, PMEL, TRPM1, TYRP1 and DCT were significantly up-regulated in brown goat skin compare with gray and white skins. PMEL showed higher expression in gray goat skin compared with white goat skin, whereas there were no significant differences in the expression of TYRP1, TRPM1 and DCT between gray and white skin samples. In addition, ELOVL3 showed higher expression in gray goat skin than in brown and white skins, whereas there was no significant differences in the expression of ELOVL3 between brown and white skin samples. These results expand our understanding of the complex molecular mechanisms of skin physiology and melanogenesis in goat and provide a foundation for future studies.

Odorants could elicit repair processes in melanized neuronal and skin cells.

The expression of ectopic olfactory receptors (ORs) in melanized cells, such as the human brain nigrostriatal dopaminergic neurons and skin melanocytes, is here pointed out. ORs are recognized to regulate skin melanogenesis, whereas OR expression in the dopaminergic neurons, characterized by accumulation of pigment neuromelanin, is downregulated in Parkinson's disease. Furthermore, the correlation between the pigmentation process and the dopamine pathway through α-synuclein expression is also highlighted. Purposely, these ORs are suggested as therapeutic target for neurodegenerative diseases related to the pigmentation disorders. Based on this evidence, a possible way of turning odorants into drugs, acting on three specific olfactory receptors, OR51E2, OR2AT4 and VN1R1, is thus introduced. Various odorous molecules are shown to interact with these ORs and their therapeutic potential against melanogenic and neurodegenerative dysfunctions, including melanoma and Parkinson's disease, is suggested. Finally, a direct functional link between olfactory and endocrine systems in human brain through VN1R1 is proposed, helping to counteract female susceptibility to Parkinson's disease in quiescent life.