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Pigment Cell & Melanoma Research Jul 2021Melanins are widely distributed in animals and plants; in vertebrates, most melanins are present on the body surface. The diversity of pigmentation in vertebrates is... (Review)
Review
Melanins are widely distributed in animals and plants; in vertebrates, most melanins are present on the body surface. The diversity of pigmentation in vertebrates is mainly attributed to the quantity and ratio of eumelanin and pheomelanin synthesis. Most natural melanin pigments in animals consist of both eumelanin and pheomelanin in varying ratios, and thus, their combined synthesis is called "mixed melanogenesis." Gene expression is an established mechanism for controlling melanin synthesis; however, there are multiple factors that affect melanin synthesis besides gene expression. Due to the differential sensitivity of the eumelanin and pheomelanin synthetic pathways to pH, melanosomal pH likely plays a major role in mixed melanogenesis. Here, we focused on various factors affecting mixed melanogenesis including (1) chemical regulation of melanin synthesis, (2) melanosomal pH regulation during normal melanogenesis and effect on mixed melanogenesis, and (3) mechanisms of melanosomal pH control (proton pumps, channels, transporters, and signaling pathways).
Topics: Animals; Cysteine; Humans; Kinetics; Melanins; Melanosomes; Monophenol Monooxygenase; Skin Pigmentation
PubMed: 33751833
DOI: 10.1111/pcmr.12970 -
International Journal of Molecular... Jun 2022The tyrosinase enzyme, which catalyzes the hydroxylation of monophenols and the oxidation of -diphenols, is typically involved in the synthesis of the dark product...
The tyrosinase enzyme, which catalyzes the hydroxylation of monophenols and the oxidation of -diphenols, is typically involved in the synthesis of the dark product melanin starting from the amino acid tyrosine. Contributing to the browning of plant and fruit tissues and to the hyperpigmentation of the skin, leading to melasma or age spots, the research of possible tyrosinase inhibitors has attracted much interest in agri-food, cosmetic, and medicinal industries. In this study, we analyzed the capability of antamanide, a mushroom bioactive cyclic decapeptide, and some of its glycine derivatives, compared to that of pseudostellarin A, a known tyrosinase inhibitor, to hinder tyrosinase activity by using a spectrophotometric method. Additionally, computational docking studies were performed in order to elucidate the interactions occurring with the tyrosinase catalytic site. Our results show that antamanide did not exert any inhibitory activity. On the contrary, the three glycine derivatives , , and , which differ from each other by the position of a glycine that substitutes phenylalanine in the parent molecule, improving water solubility and flexibility, showed tyrosinase inhibition by spectrophotometric assays. Analytical data were confirmed by computational studies.
Topics: Agaricales; Enzyme Inhibitors; Glycine; Melanins; Molecular Docking Simulation; Monophenol Monooxygenase; Peptides, Cyclic
PubMed: 35682928
DOI: 10.3390/ijms23116240 -
MBio Oct 2019Melanin is an antioxidant polyphenol pigment required for the pathogenicity of many fungal pathogens, but comprehensive regulatory mechanisms remain unidentified. In...
Melanin is an antioxidant polyphenol pigment required for the pathogenicity of many fungal pathogens, but comprehensive regulatory mechanisms remain unidentified. In this study, we systematically analyzed melanin-regulating signaling pathways in and identified four melanin-regulating core transcription factors (TFs), Bzp4, Usv101, Mbs1, and Hob1, required for induction of the laccase gene (). Bzp4, Usv101, and Mbs1 independently regulate induction, whereas Hob1 controls Bzp4 and Usv101 expression. Both Bzp4 and Usv101 are localized in the cytoplasm under nutrient-rich conditions (i.e., in the presence of yeast extract-peptone-dextrose [YPD] medium) but translocate into the nucleus upon nutrient starvation (i.e., in the presence of yeast nitrogen base [YNB] medium without glucose), and Mbs1 is constitutively localized in the nucleus. Notably, the cAMP pathway is not involved in regulation of the four TFs, but the high-osmolarity glycerol response (HOG) pathway negatively regulates induction of and Next, we searched for potential kinases upstream of the core TFs and identified nine core kinases; their deletion led to defective melanin production and induction. Deletion of or abolished induction of and and perturbed nuclear translocation of Bzp4. Notably, Gsk3 also regulated expression of , , and , indicating that it is a critical melanin-regulating kinase. Finally, an RNA sequencing-based transcriptome analysis of the wild-type strain and of Δ, Δ, Δ, and Δ strains under nutrient-rich and nutrient-starved conditions revealed that the melanin-regulating core TFs govern redundant and distinct classes of genes involved in a variety of biological processes. Melanins are dark green, brown, or black pigments that serve as antioxidant, reactive oxygen species (ROS) scavengers that protect fungal pathogens from radiation and host immune responses. , the major etiological agent of fungal meningoencephalitis, also utilizes melanin as a key virulence factor. In this basidiomycete pathogen, melanin production is regulated by the cAMP and high-osmolarity glycerol response (HOG) pathways, and yet its complex signaling networks remain poorly described. In this study, we uncovered novel melanin synthesis regulatory networks consisting of core transcription factors (TFs), including Bzp4, Usv101, Hob1, and Mbs1, and core kinases Gsk3 and Kic1. These networks were identified through coupling systematic analyses of the expression and epistatic relationships of TF and kinase mutant libraries in the presence of diverse melanin substrates with transcriptome profiling of the core TF mutants. Thus, this report provides comprehensive insight into the melanin-regulating pathways in and other fungal pathogens.
Topics: Cryptococcus neoformans; Gene Expression Profiling; Gene Expression Regulation, Fungal; Laccase; Melanins; Protein Kinases; Signal Transduction; Transcription Factors
PubMed: 31575776
DOI: 10.1128/mBio.02267-19 -
Cell Biochemistry and Biophysics Jun 2020It is believed that while eumelanin plays photoprotective and antioxidant role in pigmented tissues, pheomelanin being more photoreactive could behave as a phototoxic...
It is believed that while eumelanin plays photoprotective and antioxidant role in pigmented tissues, pheomelanin being more photoreactive could behave as a phototoxic agent. Although the metal ion-sequestering ability of melanin might be protective, transition metal ions present in natural melanins could affect their physicochemical properties. The aim of this research was to study iron binding by pheomelanin and analyze how such a binding affects selected properties of the melanin. Synthetic pheomelanin (CDM), prepared by enzymatic oxidation of DOPA in the presence of cysteine was analyzed by electron paramagnetic resonance (EPR) spectroscopy, spectrophotometry, chemical analysis, and time-resolved measurements of singlet oxygen phosphorescence. Iron broadened EPR signal of melanin and increased its optical absorption. Iron bound to melanin exhibited EPR signal at g = 4.3, typical for high-spin iron (III). Iron bound to melanin significantly altered the kinetics of melanin photodegradation, which in turn modified the accessibility and stability of the melanin-iron complexes as indicated by the release of iron from melanin induced by diethylenetriaminepentaacetic acid and KCN. Although bound to melanin iron little affects initial stages of photodegradation of CDM, the effect of iron becomes more pronounced at later stages of melanin photolysis.
Topics: Brain; Cysteine; Dihydroxyphenylalanine; Electron Spin Resonance Spectroscopy; Epidermis; Humans; Iron; Kinetics; Melanins; Oxidation-Reduction; Oxygen; Photochemistry; Photolysis; Singlet Oxygen
PubMed: 32451722
DOI: 10.1007/s12013-020-00918-1 -
Biomedicine & Pharmacotherapy =... Jun 2023Fair flawless skin is the goal for some cultures and the development of irregular skin pigmentation is considered an indication of premature skin aging. Hence, there is...
Fair flawless skin is the goal for some cultures and the development of irregular skin pigmentation is considered an indication of premature skin aging. Hence, there is a rising demand for skin whitening cosmetics. Thus, this research will be focusing on discovering the anti-pigmentation properties of Swietenia macrophylla seeds. Firstly, the seeds were extracted with ethanol and further fractionate based on their polarity before testing them on zebrafish embryos. The ethanolic extract of the seed demonstrated significant inhibition of both tyrosinase activity and melanin production in the embryos. However, after fractionation, the anti-melanogenic ability was observed to have decreased, signifying that the phytocompounds may be synergistic in nature. Still in the proteomic studies the ethanolic extract and its hexane fraction both induced the downregulation of cathepsin LB and cytoskeletal proteins that have connections to the melanogenic pathway, confirming that S. macrophylla seeds do indeed have anti-pigmentation properties that can be exploited for cosmetic use. Next, limonoids (tetranortriterpenoids found in the seed) were tested for their inhibitory effect against human tyrosinase related protein 1 (TYRP-1) via molecular docking. It was found that limonoids have a stronger binding affinity to TYRP-1 than kojic acid, suggesting that these phytocompounds may have the potential in inhibiting pigmentation. However, this still needs further confirmation before these phytocompounds can be developed into a skin whitening agent. Other assays like ex-vivo or 3D human skin culture can also be used to better study the seeds anti-pigmentation effect on humans.
Topics: Animals; Humans; Melanins; Molecular Docking Simulation; Monophenol Monooxygenase; Zebrafish; Limonins; Proteomics; Meliaceae
PubMed: 37068335
DOI: 10.1016/j.biopha.2023.114659 -
Proceedings of the National Academy of... Aug 2019Hypocretin/orexin (HCRT) and melanin concentrating hormone (MCH) neuropeptides are exclusively produced by the lateral hypothalamus and play important roles in sleep,...
Hypocretin/orexin (HCRT) and melanin concentrating hormone (MCH) neuropeptides are exclusively produced by the lateral hypothalamus and play important roles in sleep, metabolism, reward, and motivation. Loss of HCRT (ligands or receptors) causes the sleep disorder narcolepsy with cataplexy in humans and in animal models. How these neuropeptides are produced and involved in diverse functions remain unknown. Here, we developed methods to sort and purify HCRT and MCH neurons from the mouse late embryonic hypothalamus. RNA sequencing revealed key factors of fate determination for HCRT (, , , , and ) and MCH (, , and ) neurons. Loss of in mice significantly reduces HCRT and MCH cell numbers, while knock-down of a ortholog in zebrafish completely abolishes their expression, resulting in a 2-fold increase in sleep amount. We also found that loss of HCRT neurons in mice results in a specific 50% decrease in another orexigenic neuropeptide, QRFP, that might explain the metabolic syndrome in narcolepsy. The transcriptome results were used to develop protocols for the production of HCRT and MCH neurons from induced pluripotent stem cells and ascorbic acid was found necessary for HCRT and BMP7 for MCH cell differentiation. Our results provide a platform to understand the development and expression of HCRT and MCH and their multiple functions in health and disease.
Topics: Animals; Hypothalamic Hormones; Hypothalamus; Induced Pluripotent Stem Cells; Intercellular Signaling Peptides and Proteins; Melanins; Mice; Mice, Transgenic; Nerve Tissue Proteins; Neurons; Orexins; Pituitary Hormones
PubMed: 31375626
DOI: 10.1073/pnas.1902148116 -
Cells Jun 2022Melanocytes produce melanin to protect the skin from UV-B radiation. Notwithstanding, the spectrum of their functions extends far beyond their well-known role as melanin... (Review)
Review
Melanocytes produce melanin to protect the skin from UV-B radiation. Notwithstanding, the spectrum of their functions extends far beyond their well-known role as melanin production factories. Melanocytes have been considered as sensory and computational cells. The neurotransmitters, neuropeptides, and other hormones produced by melanocytes make them part of the skin's well-orchestrated and complex neuroendocrine network, counteracting environmental stressors. Melanocytes can also actively mediate the epidermal immune response. Melanocytes are equipped with ectopic sensory systems similar to the eye and nose and can sense light and odor. The ubiquitous inner circadian rhythm controls the body's basic physiological processes. Light not only affects skin photoaging, but also regulates inner circadian rhythms and communicates with the local neuroendocrine system. Do melanocytes "see" light and play a unique role in photoentrainment of the local circadian clock system? Why, then, are melanocytes responsible for so many mysterious functions? Do these complex functional devices work to maintain homeostasis locally and throughout the body? In addition, melanocytes have also been shown to be localized in internal sites such as the inner ear, brain, and heart, locations not stimulated by sunlight. Thus, what can the observation of extracutaneous melanocytes tell us about the "secret identity" of melanocytes? While the answers to some of these intriguing questions remain to be discovered, here we summarize and weave a thread around available data to explore the established and potential roles of melanocytes in the biological communication of skin and systemic homeostasis, and elaborate on important open issues and propose ways forward.
Topics: Circadian Rhythm; Epidermis; Melanins; Melanocytes; Skin
PubMed: 35805166
DOI: 10.3390/cells11132082 -
Scientific Reports Mar 2022In this study, the choroidal melanin content in healthy eyes was evaluated with polarization-sensitive optical coherence tomography (PS-OCT). We evaluated 105 healthy...
In this study, the choroidal melanin content in healthy eyes was evaluated with polarization-sensitive optical coherence tomography (PS-OCT). We evaluated 105 healthy eyes of 105 Japanese subjects. The mean thickness of melanin-containing tissue in the choroid (thickness of MeCh) and the choroidal melanin occupancy rate within a 5-mm circular region from the foveal center were calculated using the degree of polarization uniformity obtained by PS-OCT and compared with the choroidal thickness, patient age, and axial length. To evaluate regional variations, the 5-mm circular region was divided into a center area and an outer ring area, and the outer ring area was further divided into four areas (nasal, temporal, superior, and inferior). The mean thickness of MeCh showed a significant positive correlation with the choroidal thickness. The mean choroidal melanin occupancy rate showed a significant positive correlation with age. The mean choroidal melanin occupancy rate of the center area was significantly larger than that of the outer ring area. The mean thickness of MeCh and choroidal melanin occupancy rate of the nasal area were significantly lower than those of other areas. The distribution of melanin-containing tissue in the choroid varies significantly with age and location.
Topics: Choroid; Healthy Volunteers; Humans; Japan; Melanins; Tomography, Optical Coherence
PubMed: 35260673
DOI: 10.1038/s41598-022-07818-9 -
International Journal of Molecular... Aug 2020Melanogenesis is the biological and biochemical process of melanin and melanosome biosynthesis. Melanin is formed by enzymic reactions of tyrosinase family proteins that... (Review)
Review
Melanogenesis is the biological and biochemical process of melanin and melanosome biosynthesis. Melanin is formed by enzymic reactions of tyrosinase family proteins that convert tyrosine to form brown-black eumelanin and yellow-red pheomelanin within melanosomal compartments in melanocytes, following the cascades of events interacting with a series of autocrine and paracrine signals. Fully melanized melanosomes are delivered to keratinocytes of the skin and hair. The symbiotic relation of a melanocyte and an associated pool of keratinocytes is called epidermal melanin unit (EMU). Microphthalmia-associated transcription factor (MITF) plays a vital role in melanocyte development and differentiation. MITF regulates expression of numerous pigmentation genes for promoting melanocyte differentiation, as well as fundamental genes for maintaining cell homeostasis. Diseases involving alterations of EMU show various forms of pigmentation phenotypes. This review introduces four major topics of melanogenesis cascade that include (1) melanocyte development and differentiation, (2) melanogenesis and intracellular trafficking for melanosome biosynthesis, (3) melanin pigmentation and pigment-type switching, and (4) development of a novel therapeutic approach for malignant melanoma by elucidation of melanogenesis cascade.
Topics: Cell Differentiation; Humans; Melanins; Melanocytes; Melanoma; Microphthalmia-Associated Transcription Factor; Pigmentation Disorders
PubMed: 32854423
DOI: 10.3390/ijms21176129 -
Journal of Biomedical Optics Mar 2023Melanin and hemoglobin have been measured as important diagnostic indicators of facial skin conditions for aesthetic and diagnostic purposes. Commercial clinical...
SIGNIFICANCE
Melanin and hemoglobin have been measured as important diagnostic indicators of facial skin conditions for aesthetic and diagnostic purposes. Commercial clinical equipment provides reliable analysis results, but it has several drawbacks: exclusive to the acquisition system, expensive, and computationally intensive.
AIM
We propose an approach to alleviate those drawbacks using a deep learning model trained to solve the forward problem of light-tissue interactions. The model is structurally extensible for various light sources and cameras and maintains the input image resolution for medical applications.
APPROACH
A facial image is divided into multiple patches and decomposed into melanin, hemoglobin, shading, and specular maps. The outputs are reconstructed into a facial image by solving the forward problem over skin areas. As learning progresses, the difference between the reconstructed image and input image is reduced, resulting in the melanin and hemoglobin maps becoming closer to their distribution of the input image.
RESULTS
The proposed approach was evaluated on 30 subjects using the professional clinical system, VISIA VAESTRO. The correlation coefficients for melanin and hemoglobin were found to be 0.932 and 0.857, respectively. Additionally, this approach was applied to simulated images with varying amounts of melanin and hemoglobin.
CONCLUSION
The proposed approach showed high correlation with the clinical system for analyzing melanin and hemoglobin distribution, indicating its potential for accurate diagnosis. Further calibration studies using clinical equipment can enhance its diagnostic ability. The structurally extensible model makes it a promising tool for various image acquisition conditions.
Topics: Humans; Melanins; Deep Learning; Skin; Face; Hemoglobins
PubMed: 36992693
DOI: 10.1117/1.JBO.28.3.035001