Melanogenesis Associated Transcription Factor Research Articles

Transcriptional profiling of pigmentation-regulated long non-coding RNAs in the mantle of Manila clam (Ruditapes philippinarum)

Long non-coding RNAs (lncRNAs) play important roles in a variety of biological processes and have received extensive attention in recent years. However, the expression and roles of lncRNAs in the Manila clam (Ruditapes philippinarum) are still poorly understood. In this study, we identified lncRNAs in the mantle of clams with different shell colors (orange (O), zebra (Z), white (W), and white zebra (WZ)). Using poly(A)-independent and strand-specific RNA-seq, we obtained 183,818,4888 clean reads and 32,541 lncRNA transcripts. In total, 1988 lncRNAs were identified as differentially expressed lncRNAs in comparisons between six pairs of groups. Fourteen mRNAs and their target genes were found to be related to the shell color pathway of melanin and porphyrin metabolism. Protein kinase C, calmodulin, melanogenesis associated transcription factor, peroxidase-like protein, tyrosine decarboxylase, myeloperoxidase, putativetyrosinase-like protein tyr-3, dopamine beta-hydroxylase, 5-aminolevulinate synthase, tyrosine aminotransferase, uroporphyrinogen-III synthase, hephaestin, delta-aminolevulinic acid dehydratase and ferrochelatase and their corresponding 77 cis-acting lncRNAs are thought to play important roles in the melanin synthesis pathway and porphyrin metabolic pathway. This study identified the catalog of lncRNAs expressed in the mantle of Manila clam, and the results provide insights into understanding the molecular regulation of shell color and genetic breeding in R. philippinarum.

CYP27A1-dependent anti-melanoma activity of limonoid natural products targets mitochondrial metabolism

Three limonoid natural products with selective anti-proliferative activity against BRAF(V600E) and NRAS(Q61K)-mutation-dependent melanoma cell lines were identified. Differential transcriptome analysis revealed dependency of compound activity on expression of the mitochondrial cytochrome P450 oxidase CYP27A1, a transcriptional target of melanogenesis-associated transcription factor (MITF). We determined that CYP27A1 activity is necessary for the generation of a reactive metabolite that proceeds to inhibit cellular proliferation. A genome-wide small interfering RNA screen in combination with chemical proteomics experiments revealed gene-drug functional epistasis, suggesting that these compounds target mitochondrial biogenesis and inhibit tumor bioenergetics through a covalent mechanism. Our work suggests a strategy for melanoma-specific targeting by exploiting the expression of MITF target gene CYP27A1 and inhibiting mitochondrial oxidative phosphorylation in BRAF mutant melanomas.

MiR-876-5p regulates gastric cancer cell proliferation, apoptosis and migration through targeting WNT5A and MITF.

MicroRNAs (miRNAs) are reported to play critical roles in various cancers. Recently, mounting miRNAs are found to exert oncogenic or tumor inhibitory role in gastric cancer (GC), however, their potential molecular mechanism in GC remains ill-defined. Currently, we aimed to elucidate the functional and mechanistic impacts of a novel miRNA on GC cellular process. The significant down-regulation of miR-876-5p in GC cells attracted our attention. In function, we performed gain-of-function assays and found that miR-876-5p overexpression repressed proliferative, anti-apoptotic and migratory abilities and epithelial–mesenchymal transition (EMT) of GC cells. By applying bioinformatics prediction and mechanism experiments, we verified that miR-876-5p could double-bind to the 3′ untranslated regions (3′UTRs) of Wnt family member 5A (WNT5A) and melanogenesis associated transcription factor (MITF), thus regulating their mRNA and protein levels. Both WNT5A and MITF were highly expressed in GC cells. Additionally, we conducted loss-of-function assays and confirmed the oncogenic roles of WNT5A and MITF in GC. Finally, rescue assay uncovered a fact that miR-876-5p suppressed GC cell viability and migration, but induced cell apoptosis via targeting WNT5A and MITF. Taken together, we might offer a valuable evidence for miR-876-5p role in GC development.

MDA-7/IL-24 regulates the miRNA processing enzyme DICER through downregulation of MITF

Melanoma differentiation-associated gene-7/interleukin-24 (mda-7/IL-24) is a multifunctional cytokine displaying broad-spectrum anticancer activity in vitro or in vivo in preclinical animal cancer models and in a phase 1/2 clinical trial in patients with advanced cancers. mda-7/IL-24 targets specific miRNAs, including miR-221 and miR-320, for down-regulation in a cancer-selective manner. We demonstrate that mda-7/IL-24, administered through a replication incompetent type 5 adenovirus (Ad.mda-7) or with His-MDA-7/IL-24 protein, down-regulates DICER, a critical regulator in miRNA processing. This effect is specific for mature miR-221, as it does not affect Pri-miR-221 expression, and the DICER protein, as no changes occur in other miRNA processing cofactors, including DROSHA, PASHA, or Argonaute. DICER is unchanged by Ad.mda-7/IL-24 in normal immortal prostate cells, whereas Ad.mda-7 down-regulates DICER in multiple cancer cells including glioblastoma multiforme and prostate, breast, lung, and liver carcinoma cells. MDA-7/IL-24 protein down-regulates DICER expression through canonical IL-20/IL-22 receptors. Gain- and loss-of-function studies confirm that overexpression of DICER rescues deregulation of miRNAs by mda-7/IL-24, partially rescuing cancer cells from mda-7/IL-24-mediated cell death. Stable overexpression of DICER in cancer cells impedes Ad.mda-7 or His-MDA-7/IL-24 inhibition of cell growth, colony formation, PARP cleavage, and apoptosis. In addition, stable overexpression of DICER renders cancer cells more resistant to Ad.mda-7 inhibition of primary and secondary tumor growth. MDA-7/IL-24-mediated regulation of DICER is reactive oxygen species-dependent and mediated by melanogenesis-associated transcription factor. Our research uncovers a distinct role of mda-7/IL-24 in the regulation of miRNA biogenesis through alteration of the MITF-DICER pathway.

A non‐coding regulatory variant in the 5′‐region of the MITF gene is associated with white‐spotted coat in Brown Swiss cattle

Recently, the Swiss breeding association reported an increasing number of white-spotted cattle in the Brown Swiss breed, which is normally solid brown coloured. A total of 60 Brown Swiss cattle with variably sized white abdominal spots, facial markings and depigmented claws were collected for this study. A genome-wide association study using 40k SNP genotypes of 20 cases and 1619 controls enabled us to identify an associated genome region on chromosome 22 containing the MITF gene, encoding the melanogenesis associated transcription factor. Variants at the MITF locus have been reported before to be associated with white or white-spotted phenotypes in other species such as horses, dogs and mice. Whole-genome sequencing of a single white-spotted cow and subsequent genotyping of 172 Brown Swiss cattle revealed two significantly associated completely linked single nucleotide variants (rs722765315 and rs719139527). Both variants are located in the 5'-regulatory region of the bovine MITF gene, and comparative sequence analysis showed that the variant rs722765315, located 139kb upstream of the transcription start site of the bovine melanocyte-specific MITF transcript, is situated in a multi-species conserved sequence element which is supposed to be regulatory important. Therefore, we hypothesize that rs722765315 represents the most likely causative variant for the white-spotting phenotype observed in Brown Swiss cattle. Presence of the mutant allele in a heterozygous or homozygous state supports a dominant mode of inheritance with incomplete penetrance and results in a variable extent of coat colour depigmentation.

AKT inhibition-mediated dephosphorylation of TFE3 promotes overactive autophagy independent of MTORC1 in cadmium-exposed bone mesenchymal stem cells

ABSTRACTCadmium (Cd) is a toxic metal that is widely found in numerous environmental matrices and induces serious adverse effects in various organs and tissues. Bone tissue seems to be a crucial target of Cd contamination. Macroautophagy/autophagy has been proposed to play a pivotal role in Cd-mediated bone toxicity. However, the mechanisms that underlie Cd-induced autophagy are not yet completely understood. We demonstrated that Cd treatment increased autophagic flux and inhibition of the autophagic process using Atg7 gene silencing blocked the Cd-induced mesenchymal stem cell death. Mechanistically, Cd activated nuclear translocation of TFE3 but not that of TFEB or MITF, which contributed to the expression of autophagy-related genes and lysosomal biogenesis. Specifically, Cd decreased expression of phospho-AKT (Ser473). The reduction in AKT activity led to dephosphorylation of cytosolic TFE3 at Ser565 and promoted TFE3 nuclear translocation independently of MTORC1. Notably, Cd treatment increased the activity of PPP3/calcineurin, and pharmacological inhibition of PPP3/calcineurin with FK506 suppressed AKT dephosphorylation and TFE3 activity. These results suggest that PPP3/calcineurin negatively regulates AKT phosphorylation and is involved in Cd-induced TFE3-dependent autophagy. Modulation of the PPP3/calcineurin-AKT-TFE3 autophagic-lysosomal machinery may offer novel therapeutic approaches for the treatment of Cd-induced bone damage.Abbreviations: ACTB: actin: beta; AKT: thymoma viral proto-oncogene; AMPK: AMP-activated protein kinase; ATG: autophagy related; Baf A1: bafilomycin A1; Cd: cadmium; FOXO3: forkhead box O3; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MITF: melanogenesis associated transcription factor; MSC: mesenchymal stem sell; MTORC1: mechanistic target of rapamycin kinase complex 1; RPS6KB1: ribosomal protein S6 kinase: polypeptide 1; SGK1: serum/glucocorticoid regulated kinase 1; SQSTM1/p62: sequestosome 1;TFE3: transcription factor E3; TFEB: transcription factor EB; TFEC: transcription factor EC

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

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.

A direct link between MITF, innate immunity, and hair graying.

Melanocyte stem cells (McSCs) and mouse models of hair graying serve as useful systems to uncover mechanisms involved in stem cell self-renewal and the maintenance of regenerating tissues. Interested in assessing genetic variants that influence McSC maintenance, we found previously that heterozygosity for the melanogenesis associated transcription factor, Mitf, exacerbates McSC differentiation and hair graying in mice that are predisposed for this phenotype. Based on transcriptome and molecular analyses of Mitfmi-vga9/+ mice, we report a novel role for MITF in the regulation of systemic innate immune gene expression. We also demonstrate that the viral mimic poly(I:C) is sufficient to expose genetic susceptibility to hair graying. These observations point to a critical suppressor of innate immunity, the consequences of innate immune dysregulation on pigmentation, both of which may have implications in the autoimmune, depigmenting disease, vitiligo.

Isolation and characterization of circulating melanoma cells by size filtration and fluorescent in-situ hybridization.

Isolation of circulating tumor cells (CTCs) from blood of melanoma patients has been difficult owing to inconsistent expression of surface antigens. Here we report on the isolation, detection, and characterization of CTCs from blood of melanoma patients using microfiltration and fluorescent in-situ hybridization (FISH). Two tubes of blood from 15 patients with advanced melanoma were collected. These two tubes subsequently underwent filtration through a membrane with pore sizes of 7.5 μm. Isolated cells from one tube were analyzed by FISH for RREB1 (6p24), MYB (6q32), SE6 (D6Z1), and CCND1 (11q13) and the other paired specimen was analyzed by immunofluorescence for HMB45, melanoma-associated antigen recognized by T cells-1, tyrosinase and melanogenesis associated transcription factor. We identified CTCs in 10 out of 13 melanoma samples by immunofluorescence (2.5-99 CTCs/3 ml of blood) and in 13 specimens by FISH (7.2-76 CTCs/3 ml of blood) with more CTCs identified by FISH in 10 out 13 samples. Two filters failed. Our results show that CTCs are detectable in the majority of patients with advanced melanoma. These tools will be useful in characterizing treatment related changes of melanoma in CTCs.

TRP‑2 mediates coat color pigmentation in sheep skin.

Tyrosinase-related protein 2 (TRP-2) is one of the most important members of the tyrosinase family, and is a key enzyme involved in melanin biosynthesis. In the present study, a skin transcriptome profile, immunohistochemistry, western blotting and reverse transcription-quantitative polymerase chain reaction were used to investigate TRP-2 expression in sheep with different coat colors, namely, black, white and black-white. TRP-2 was overexpressed in melanocytes in order to study the effect of TRP-2 on melanin production. Results revealed differing TRP-2 levels in sheep of different coat colors and in various parts of the coat with different colors in the same sheep. TRP-2 expression levels in dark-colored areas were significantly increased compared with light-colored areas in piebald sheep. TRP-2 overexpression may regulate melanogenesis and significantly increase melanogenesis associated transcription factor expression in vitro. Therefore, TRP-2 may affect melanin production in sheep, and different expression levels determine coat color. The results may provide novel approaches for developing therapeutic strategies for skin diseases associated with pigmentation disorders.

Finasteride inhibits melanogenesis through regulation of the adenylate cyclase in melanocytes and melanoma cells

Finasteride is a well-known 5α-reductase inhibitor used for treatment of alopecia and prostate cancer. But the effect of finasteride in regulating melanogenesis is still unclear. In the present study the role of finasteride on melanogenesis was investigated. Finasteride decrease melanin level in melanocyte melan-a cells and B16F10 melanoma cells without inducing cytotoxicity. MC1R (melanocortin 1 receptor) protein expression was also inhibited by finasteride thereby decreasing the expression of adenylate cyclase, MITF (Melanogenesis associated transcription factor), tyrosinases, TRP (tyrosinase-related protein) -1 and -2. Thus our study suggest that finasteride inhibits melanogenesis in melanocyte and melanoma cells by inhibiting MC1R.

Annona muricata L. extracts decrease melanogenesis in B16F10 mouse melanoma cells

BackgroundAnnona muricata (A. muricata) L. (also known as graviola) contains various antioxidants that have beneficial effects on headaches, hypertension, coughs and asthma. A. muricata L. also has various other physiological effects, such as antispasmodic effects for the treatment of heart conditions, and sedative and nervine effects. In the present study, the effect of A. muricata L. extracts on melanogenesis was investigated and the ensuing inhibitory mechanisms were determined.MethodsThe inhibitory effects of A. muricata L. extracts on melanogenesis were initially investigated by measuring melanin contents. Subsequently, the ensuing mechanisms were characterized by determining changes in the activity of tyrosinase, which is the rate-limiting step of melanogenesis. Finally, mRNA and protein expression levels of tyrosinase and the melanogenesis-associated transcription factor (MITF) were determined.ResultsDecreased melanin contents after treatments with A. muricata L. extracts suggested skin-whitening effects, and these changes were reflected by decreased tyrosinase activities. In addition, tyrosinase mRNA and protein expression levels were regulated by A. muricata L. extracts. MITF is a known key transcription factor of tyrosinase and was transcriptionally regulated by A. muricata L. extracts. Specifically, MITF mRNA expression levels were decreased in the presence of A. muricata L. extracts. Taken together, the melanogenesis-moderating effects of A. muricata L. extracts follow suppression of MITF mRNA expression and subsequent transactivation of tyrosinase.ConclusionsThe results of the present study confirm the skin-whitening effects of A. muricata L. and characterize the related molecular mechanisms. These data indicate that A. muricata L. has high potential as an ingredient of skin-whitening cosmetics.

Prenatal diagnosis and genetic counseling�for Waardenburg syndrome type�I and II in Chinese families

Waardenburg syndrome (WS) is an auditory-pigmentary disorder with varying combinations of sensorineural hearing loss and abnormal pigmentation. The present study aimed to investigate the underlying molecular pathology and provide a method of prenatal diagnosis of WS in Chinese families. A total of 11 patients with WS from five unrelated Chinese families were enrolled. A thorough clinical examination was performed on all participants. Furthermore, patients with WS underwent screening for mutations in the following genes: Paired box 3 (PAX3), melanogenesis associated transcription factor (MITF), SRY-box 10, snail family transcriptional repressor 2 and endothelin receptor type B using polymerase chain reaction sequencing. Array-based comparative genomic hybridization was used for specific patients whose sequence results were normal. Following identification of the genotype of the probands and their parents, prenatal genetic diagnosis was performed for family 01 and 05. According to the diagnostic criteria for WS, five cases were diagnosed as WS1, while the other six cases were WS2. Genetic analysis revealed three mutations, including a nonsense mutation PAX3 c.583C>T in family 01, a splice-site mutation MITF c.909G>A in family 03 and an in-frame deletion MITF c.649_651delGAA in family 05. To the best of the authors' knowledge the mutations (c.583C>T in PAX3 and c.909G>A in MITF) were reported for the first time in Chinese people. Mutations in the gene of interest were not identified in family 02 and 04. The prenatal genetic testing of the two fetuses was carried out and demonstrated that the two babies were normal. The results of the present study expanded the range of known genetic mutations in China. Identification of genetic mutations in these families provided an efficient way to understand the causes of WS and improved genetic counseling.

Melanogenesis in uveal melanoma cells: Effect of argan oil.

The mechanisms underlying cutaneous melanogenesis have been widely studied; however, very little is known about uveal melanogenesis. Melanin is normally produced by uveal melanocytes and gives the color to the iris. A derangement from this normal production may occur, for instance, by iatrogenic events, such as glaucoma therapy with prostaglandins that may enhance cutaneous and iris pigmentation. In this study, we investigated the mechanisms that regulate uveal melanogenesis in human uveal melanoma cells(92.1) and murine cutaneous melanoma cells(B16-F1). In the first part of the study, we compared the effects of known cutaneous pigmenting agents on the B16-F1 and 92.1 cells, showing an opposite response of the two cell lines. Subsequently, using argan oil, a known depigmenting agent for murine cutaneous melanoma cells, on 92.1 cells, we found that in these cells, it also functioned as an inhibitor of melanogenesis and tyrosinase expression. From a molecular perspective, treatment of the 92.1cells with argan oil decreased melanogenesis-associated transcription factor(MITF) gene expression by inducing MITF phosphorylation at Ser73, thus leading to MITF ubiquitination and disposal. It also led to the downregulation of the extracellular signal-regulated kinase(ERK)1/2 and Akt pathways, also known to be involved in cutaneous melanogenesis, although with an opposing function. Taken together, our data indicate that: ⅰ)some differences exist in the regulation of melanogenesis between cutaneous and uveal melanoma cells; and ⅱ)argan oil exerts a depigmenting effect on 92.1cells through its action on the ERK1/2 and Akt pathways.

Identification of polymorphisms in MITF and DCT genes and their associations with plumage colors in Asian duck breeds.

ObjectiveThe aim of this study was to investigate the effect of single nucleotide polymorphisms (SNPs) of the melanogenesis associated transcription factor (MITF) and dopachrome tautomerase (DCT) genes on plumage coloration in Asian native duck breeds. MITF encodes a protein for microphthalmia-associated transcription factor, which regulates the development and function of melanocytes for pigmentation of skin, hair, and eyes. Among the tyrosinase-related family genes, DCT is a pigment cell-specific gene that plays important roles in the melanin synthesis pathway and the expression of skin, feather, and retina color.MethodsFive Asian duck varieties (black Korean native, white Korean native, commercial Peking, Nageswari, and Bangladeshi Deshi white ducks) were investigated to examine the polymorphisms associated with plumage colors. Among previously identified SNPs, three synonymous SNPs and one indel of MITF and nine SNPs in exon regions of DCT were genotyped. The allele frequencies for SNPs of the black and white plumage color populations were estimated and Fisher’s exact test was conducted to assess the association between the allele frequencies of these two populations.ResultsTwo synonymous SNPs (c.114T>G and c.147T>C) and a 14-bp indel (GCTGCAAAC AGATG) in intron 7 of MITF were significantly associated with the black- and white-colored breeds (p<0.001). One non-synonymous SNP [c.938A>G (p.His313Arg)] in DCT, was highly significantly associated (p<0.001) and a synonymous SNP (c.753A>G) was significantly associated (p<0.05) with black and white color plumage in the studied duck populations.ConclusionThe results of this study provide a basis for further investigations of the associations between polymorphisms and plumage color phenotypes in Asian duck breeds.

Advances in the diagnosis of hereditary kidney cancer: Initial results of a multigene panel test

Panel testing has been recently introduced to evaluate hereditary cancer; however, limited information is available regarding its use in kidney cancer. The authors retrospectively reviewed test results and clinical data from patients who underwent targeted multigene panel testing of up to 19 genes associated with hereditary kidney cancer from 2013 to 2016. The frequency of positive (mutation/variant likely pathogenic), inconclusive (variant of unknown significance), and negative results was evaluated. A logistic regression analysis evaluated predictive factors for a positive test. Patients (n = 1235) had a median age at diagnosis of 46 years, which was significantly younger than the US population of individuals with kidney cancer (P < .0001). Overall, 6.1%, 75.5%, and 18.4% of individuals had positive, negative, and inconclusive results, respectively. The most commonly altered genes included folliculin (FLCN) and fumarate hydratase (FH), which were altered in 1.8% and 1.3% of patients, respectively. Tuberous Sclerosis Complex 2 (TSC2), mesenchymal epithelial transition factor proto-oncogene (MET), and PMS1 homolog 2 (PMS2) had the highest rates of variants of unknown significance, which were identified in 2.7%, 2.2%, and 1.7% of patients, respectively. Early age of onset was the only factor that was identified as predictive of a positive test on multivariate analysis (odds ratio, 0.975; P = .0052) and may be the only identifying characteristic of low-penetrant syndromes, such as those associated with MITF (melanogenesis-associated transcription factor) mutations, which do not have singular histology or a family history of kidney cancer. Panel tests may be particularly useful for patients who lack distinguishing clinical characteristics of known hereditary kidney cancer syndromes. The current results support the use of early age of onset for genetic counseling and/or testing. Cancer 2017;123:4363-71. © 2017 American Cancer Society.

What's in a name?

We humans love to name things, be they living or inanimate. Names help us as a mental short cut, so that when we refer to an object or a living being we do not have to resort to lengthy descriptions of their attributes. Names simplify and smoothen our conversations. Many names directly reflect specific characteristics of the named, such as “eumelanin” (from Greek ευ = good, true, and μελασ = black, dark), but others are entirely devoid of any inner meaning. A typical example for this latter group is “q” for the long arm of a human chromosome. That does not mean, however, that the choice of “q” does not have its history. As the story is told, battles raged at a Chicago conference in 1966 about how to name the chromosome arms. Some argued for “s” and “l” (for short and long). The German-born American geneticist Klaus Patau, of fame for having discovered the cytogenetic basis of trisomy 13, argued that the short arm should be called “k” (for kurz, German for short), but the French geneticist Jérôme Jean Louis Marie Lejeune, of fame for having co-discovered the cytogenetic basis of Down syndrome, strongly argued for “p” (for petit, French for short). Nevertheless, the common “l” (for English long; French long; or German lang) could be confused with “1,” and so Lionel Penrose, a British psychiatrist and medical geneticist who is known, among many other things, for having associated the risk for Down syndrome with maternal age, proposed a compromise: “p” and “q,” simply because “q” followed “p” in the alphabet and perhaps because p + q = 1 (one chromosome), in allusion to the Hardy-Weinberg equilibrium, where the frequency of the dominant allele p + the frequency of the recessive allele q also equals 1. Why do I write about these hard-fought battles of a distant past? Well, HUGO, the Human Genome Organization, recently redefined MITF, a gene dear to our hearts. They now call it “melanogenesis-associated transcription factor” instead of the well-known “microphthalmia-associated transcription factor.” We all agree, of course, that MITF mutations cause microphthalmia (=small eyes) only in mice and not usually in humans or many of the other species in which its homologues are found. But neither do MITF mutations just cause deficiencies in melanogenesis. No, MITF is a jack-of-all-trades, involved in many physiological processes in melanocytes and melanoma, which include the regulation of cell proliferation, autophagy, and even DNA repair. It also operates in many other cell types, such as in osteoclasts and mast cells, and in a variety of organs, such as kidneys and, in Drosophila, the gut. It is called microphthalmia-associated transcription factor for purely historical reasons. The corresponding locus was discovered in mice by Paula Hertwig in 1942 (for a short description, see PCMR 23, 729–735, 2010). She originally named it “m” for microphthalmia, perhaps because the small-eye phenotype seemed the most unusual to her or because the original cross also segregated an allele for albino, which independently made some offspring white (though not microphthalmic). Hans Grüneberg, the eminent mouse geneticist, then proposed the symbol “mi” because “m” was already taken for another locus, misty. The cloning of the mi gene was reported in 1993 and in negotiations with the International Committee on Standardized Genetic Nomenclature for Mice and HUGO, we later named it Mitf rather than “Mi” because gene names required at least four letters and because it indeed encoded a transcription factor. Redefining it now as “melanogenesis-associated transcription factor” obfuscates this historical context and replaces an admittedly restricted definition with one that is equally restricted. This is totally unnecessary, only creates confusion for people working with different species, and does a disservice to the gene's interesting history of discovery and analysis. Hence, I urge everyone working in this area to ignore HUGO's unenlightened redefinition and continue using the established term. After all, as Eirikur Steingrimsson has pointed out, if one really wanted to be consequential, using the term “melanogenesis-associated transcription factor” would also require a renaming of the gene from MITF to METF, a change even HUGO did not have the courage to propose!

Applications of Panax ginseng leaves-mediated gold nanoparticles in cosmetics relation to antioxidant, moisture retention, and whitening effect on B16BL6 cells

BackgroundBioactive compounds in plant extracts are able to reduce metal ions to nanoparticles through the process of green synthesis. Panax ginseng is an oriental medicinal herb and an adaptogen which has been historically used to cure various diseases. In addition, the P. ginseng leaves-mediated gold nanoparticles are the value-added novel materials. Its potential as a cosmetic ingredient is still unexplored. The aim of this study was to evaluate the antioxidant, moisture retention and whitening properties of gold nanoparticles (PgAuNPs) in cosmetic applications. MethodsCell-free experiments were performed to evaluate PgAuNP's antioxidant and moisture retention properties and inhibition activity on mushroom tyrosinase. Furthermore, in vitro cell cytotoxicity was evaluated using normal human dermal fibroblast and murine B16BL6 melanoma cells (B16) after treatment with increasing concentrations of PgAuNPs for 24 h, 48 h, and 72 h. Finally, in vitro cell assays on B16 cells were performed to evaluate the whitening effect of PgAuNPs through reduction of cellular melanin content and tyrosinase activity. ResultsIn vitro DPPH radical scavenging assay results revealed that PgAuNPs exhibited antioxidant activity in a dose-dependent manner. PgAuNPs exhibited moisture retention capacity and effectively inhibited mushroom tyrosinase. In addition, 3-(4,5-dimethyl-thiazol-2yl)-2,5-diphenyl tetrazolium bromide results revealed that PgAuNPs were not toxic to human dermal fibroblast and B16 cells; in addition, they significantly reduced melanin content, tyrosinase activity, and mRNA expression of melanogenesis-associated transcription factor and tyrosinase in B16 cells. ConclusionOur study is the first report to provide evidence supporting that P. ginseng leaves-capped gold nanoparticles could be used as multifunctional ingredients in cosmetics.