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Postepy Higieny I Medycyny... Jun 2016Melanins are natural pigments of skin, hair and eyes and can be classified into two main types: brown to black eumelanin and yellow to reddish-brown pheomelanin.... (Review)
Review
Melanins are natural pigments of skin, hair and eyes and can be classified into two main types: brown to black eumelanin and yellow to reddish-brown pheomelanin. Biosynthesis of melanins takes place in melanosomes, which are specialized cytoplasmic organelles of melanocytes - dendritic cells located in the basal layer of the epidermis, uveal tract of the eye, hair follicles, as well as in the inner ear, central nervous system and heart. Melanogenesis is a multistep process and begins with the conversion of amino acid L-tyrosine to DOPAquinone. The addition of cysteine or glutathione to DOPAquinone leads to the intermediates formation, followed by subsequent transformations and polymerization to the final product, pheomelanin. In the absence of thiol compounds DOPAquinone undergoes an intramolecular cyclization and oxidation to form DOPAchrome, which is then converted to 5,6-dihydroksyindole (DHI) or 5,6-dihydroxyindole-2-carboxylic acid (DHICA). Eumelanin is formed by polymerization of DHI and DHICA and their quinones. Regulation of melanogenesis is achieved by physical and biochemical factors. The article presents the intracellular signaling pathways: cAMP/PKA/CREB/MITF cascade, MAP kinases cascade, PLC/DAG/PKCβ cascade and NO/cGMP/PKG cascade, which are involved in the regulation of expression and activity of the melanogenesis-related proteins by ultraviolet radiation and endogenous agents (cytokines, hormones). Activity of the key melanogenic enzyme, tyrosinase, is also affected by pH and temperature. Many pharmacologically active substances are able to inhibit or stimulate melanin biosynthesis, as evidenced by in vitro studies on cultured pigment cells.
Topics: Animals; Benzoquinones; Cytokines; Dihydroxyphenylalanine; Gene Expression Regulation, Enzymologic; Hormones; Humans; Indolequinones; Indoles; Melanins; Melanosomes; Monophenol Monooxygenase; Signal Transduction; Tyrosine; Ultraviolet Rays
PubMed: 27356601
DOI: 10.5604/17322693.1208033 -
Molecules (Basel, Switzerland) Aug 2022Nicotinamide nucleotide transhydrogenase (NNT) is involved in decreasing melanogenesis through tyrosinase degradation induced by cellular redox changes. Nicotinamide is...
Nicotinamide nucleotide transhydrogenase (NNT) is involved in decreasing melanogenesis through tyrosinase degradation induced by cellular redox changes. Nicotinamide is a component of coenzymes, such as NAD, NADH, NADP, and NADPH, and its levels are modulated by NNT. Vitamin C and polydeoxyribonucleotide (PDRN) are also known to decrease skin pigmentation. We evaluated whether a mixture of nicotinamide, vitamin C, and PDRN (NVP-mix) decreased melanogenesis by modulating mitochondrial oxidative stress and NNT expression in UV-B-irradiated animals and in an in vitro model of melanocytes treated with conditioned media (CM) from UV-B-irradiated keratinocytes. The expression of NNT, GSH/GSSG, and NADPH/NADP in UV-B-irradiated animal skin was significantly decreased by UV-B radiation but increased by NVP-mix treatment. The expression of NNT, GSH/GSSG, and NADPH/NADP ratios decreased in melanocytes after CM treatment, although they increased after NVP-mix administration. In NNT-silenced melanocytes, the GSH/GSSG and NADPH/NADP ratios were further decreased by CM compared with normal melanocytes. NVP-mix decreased melanogenesis signals, such as MC1R, MITF, TYRP1, and TYRP2, and decreased melanosome transfer-related signals, such as RAB32 and RAB27A, in UV-B-irradiated animal skin. NVP-mix also decreased MC1R, MITF, TYRP1, TYRP2, RAB32, and RAB27A in melanocytes treated with CM from UV-irradiated keratinocytes. The expression of MC1R and MITF in melanocytes after CM treatment was unchanged by NNT silencing. However, the expression of TYRP1, TYRP2, RAB32, and RAB27A increased in NNT-silenced melanocytes after CM treatment. NVP-mix also decreased tyrosinase activity and melanin content in UV-B-irradiated animal skin and CM-treated melanocytes. In conclusion, NVP-mix decreased mitochondrial oxidative stress by increasing NNT expression and decreased melanogenesis by decreasing MC1R/MITF, tyrosinase, TYRP1, and TYRP2.
Topics: Animals; Ascorbic Acid; Glutathione Disulfide; Melanins; Melanocytes; Monophenol Monooxygenase; NADP; NADP Transhydrogenases; Niacinamide; Polydeoxyribonucleotides; Vitamins
PubMed: 35956878
DOI: 10.3390/molecules27154923 -
Developmental and Comparative Immunology Sep 2021Melanin production from different types of phenoloxidases (POs) confers immunity from a variety of pathogens ranging from viruses and microorganisms to parasites. The... (Review)
Review
Melanin production from different types of phenoloxidases (POs) confers immunity from a variety of pathogens ranging from viruses and microorganisms to parasites. The arthropod proPO expresses a variety of activities including cytokine, opsonin and microbiocidal activities independent of and even without melanin production. Proteolytic processing of proPO and its activating enzyme gives rise to several peptide fragments with a variety of separate activities in a process reminiscent of vertebrate complement system activation although proPO bears no sequence similarity to vertebrate complement factors. Pathogens influence proPO activation and thereby what types of immune effects that will be produced. An increasing number of specialised pathogens - from parasites to viruses - have been identified who can synthesise compounds specifically aimed at the proPO-system. In invertebrates outside the arthropods phylogenetically unrelated POs are participating in melanization reactions obviously aimed at intruders and/or aberrant tissues.
Topics: Animals; Arthropods; Bacteria; Cell Proliferation; Enzyme Activation; Enzyme Precursors; Fungi; Hemocytes; Immunity, Innate; Melanins; Monophenol Monooxygenase; Receptors, Pattern Recognition; Viruses
PubMed: 33857469
DOI: 10.1016/j.dci.2021.104098 -
Molecules (Basel, Switzerland) Apr 2022Skin hyperpigmentation resulting from excessive tyrosinase expression has long been a problem for beauty lovers, which has not yet been completely solved. Although... (Review)
Review
Skin hyperpigmentation resulting from excessive tyrosinase expression has long been a problem for beauty lovers, which has not yet been completely solved. Although researchers are working on finding effective tyrosinase inhibitors, most of them are restricted, due to cell mutation and cytotoxicity. Therefore, functional foods are developing rapidly for their good biocompatibility. Food-derived peptides have been proven to display excellent anti-tyrosinase activity, and the mechanisms involved mainly include inhibition of oxidation, occupation of tyrosinase's bioactive site and regulation of related gene expression. For anti-oxidation, peptides can interrupt the oxidative reactions catalyzed by tyrosinase or activate an enzyme system, including SOD, CAT, and GSH-Px to scavenge free radicals that stimulate tyrosinase. In addition, researchers predict that peptides probably occupy the site of the substrate by chelating with copper ions or combining with surrounding amino acid residues, ultimately inhibiting the catalytic activity of tyrosinase. More importantly, peptides reduce the tyrosinase expression content, primarily through the cAMP/PKA/CREB pathway, with PI3K/AKT/GSK3β, MEK/ERK/MITF and p38 MAPK/CREB/MITF as side pathways. The objective of this overview is to recap three main mechanisms for peptides to inhibit tyrosinase and the emerging bioinformatic technologies used in developing new inhibitors.
Topics: Cell Line, Tumor; Humans; Hypopigmentation; Melanins; Microphthalmia-Associated Transcription Factor; Monophenol Monooxygenase; Phosphatidylinositol 3-Kinases; Signal Transduction
PubMed: 35566061
DOI: 10.3390/molecules27092710 -
Journal of Enzyme Inhibition and... Dec 2019Tyrosinase is a key enzyme involved in melanin synthesis. Therefore, various tyrosinase inhibitors have been screened by researchers in recent years. In the present...
Tyrosinase is a key enzyme involved in melanin synthesis. Therefore, various tyrosinase inhibitors have been screened by researchers in recent years. In the present study, we discovered a novel tyrosinase inhibitor, a peptide ECGYF (named EF-5), with free radical scavenging ability. The effect of tyrosinase inhibition by EF-5 was stronger than that of arbutin and glutathione, when analyzed both (IC50: 0.46 mM) and . The UV-Vis absorption and circular dichroism spectroscopies indicated that EF-5 interacted with tyrosinase in a different way as that of glutathione. The results of molecular docking showed that the binding between EF-5 and tyrosinase was determined majorly by hydrogen bonds and hydrophobic interactions. EF-5 had also retained its ability to scavenge both hydroxyl and superoxide radicals and was found to be nontoxic to cells, as revealed by the MTT assay. These features suggested that the EF-5 peptide may serve as a safe and effective alternative as a tyrosinase inhibitor.
Topics: Dose-Response Relationship, Drug; Enzyme Inhibitors; Free Radical Scavengers; Humans; Molecular Docking Simulation; Molecular Structure; Monophenol Monooxygenase; Peptides; Structure-Activity Relationship; Tumor Cells, Cultured
PubMed: 31496313
DOI: 10.1080/14756366.2019.1661401 -
Journal of Agricultural and Food... Aug 2018Rice-bran albumin (RBAlb), which shows higher tyrosinase-inhibitory activity than other protein fractions, was hydrolyzed with papain to improve the bioactivity. The...
Rice-bran albumin (RBAlb), which shows higher tyrosinase-inhibitory activity than other protein fractions, was hydrolyzed with papain to improve the bioactivity. The obtained RBAlb hydrolysate (RBAlbH) was separated into 11 peptide fractions by RP-HPLC. Tyrosinase inhibition and copper chelation activities decreased with increasing retention times of the peptide fractions. RBAlbH fraction 1, which exhibited the greatest activity, contained 13 peptides whose sequences were determined by using LC-MS/MS. Most of the peptide sequences contained features of previously reported tyrosinase-inhibitory and metal-chelating peptides, especially peptide SSEYYGGEGSSSEQGYYGEG. RBAlbH fraction 1 showed more effective tyrosinase inhibition (IC = 1.31 mg/mL) than citric acid (IC = 9.38 mg/mL), but it was less effective than ascorbic acid (IC = 0.03 mg/mL, P ≤ 0.05). It showed copper-chelating activity (IC = 0.62 mg/mL) stronger than that of EDTA (IC = 1.06 mg/mL, P ≤ 0.05). These results suggest that RBAlbH has potential as a natural tyrosinase inhibitor and copper chelator for application in the food and cosmetic industries.
Topics: Albumins; Amino Acid Sequence; Chelating Agents; Copper; Enzyme Inhibitors; Hydrolysis; Monophenol Monooxygenase; Oryza; Peptides; Plant Proteins; Seeds
PubMed: 30016586
DOI: 10.1021/acs.jafc.8b01849 -
International Journal of Molecular... Mar 2022The three-dimensional structure of tyrosinase has been crystallized from many species but not from Homo sapiens. Tyrosinase is a key enzyme in melanin biosynthesis,...
The three-dimensional structure of tyrosinase has been crystallized from many species but not from Homo sapiens. Tyrosinase is a key enzyme in melanin biosynthesis, being an important target for melanoma and skin-whitening cosmetics. Several studies employed the structure of tyrosinase from as a model enzyme. Recently, 98% of human genome proteins were elucidated by AlphaFold. Herein, the AlphaFold structure of human tyrosinase and the previous model were compared. Moreover, tyrosinase-related proteins 1 and 2 were included, along with inhibition studies employing kojic and cinnamic acids. Peptides are widely studied for their inhibitory activity of skin-related enzymes. Cyanophycin is an amino acid polymer produced by cyanobacteria and is built of aspartic acid and arginine; arginine can be also replaced by other amino acids. A new set of cyanophycin-derived dipeptides was evaluated as potential inhibitors. Aspartate-glutamate showed the strongest interaction and was chosen as a leading compound for future studies.
Topics: Arginine; Bacterial Proteins; Dipeptides; Enzyme Inhibitors; Humans; Molecular Docking Simulation; Monophenol Monooxygenase
PubMed: 35328756
DOI: 10.3390/ijms23063335 -
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 -
Proceedings of the National Academy of... Oct 2023Most biocatalytic processes in eukaryotic cells are regulated by subcellular microenvironments such as membrane-bound or membraneless organelles. These natural...
Most biocatalytic processes in eukaryotic cells are regulated by subcellular microenvironments such as membrane-bound or membraneless organelles. These natural compartmentalization systems have inspired the design of synthetic compartments composed of a variety of building blocks. Recently, the emerging field of liquid-liquid phase separation has facilitated the design of biomolecular condensates composed of proteins and nucleic acids, with controllable properties including polarity, diffusivity, surface tension, and encapsulation efficiency. However, utilizing phase-separated condensates as optical sensors has not yet been attempted. Here, we were inspired by the biosynthesis of melanin pigments, a key biocatalytic process that is regulated by compartmentalization in organelles, to design minimalistic biomolecular condensates with emergent optical properties. Melanins are ubiquitous pigment materials with a range of functionalities including photoprotection, coloration, and free radical scavenging activity. Their biosynthesis in the confined melanosomes involves oxidation-polymerization of tyrosine (Tyr), catalyzed by the enzyme tyrosinase. We have now developed condensates that are formed by an interaction between a Tyr-containing peptide and RNA and can serve as both microreactors and substrates for tyrosinase. Importantly, partitioning of Tyr into the condensates and subsequent oxidation-polymerization gives rise to unique optical properties including far-red fluorescence. We now demonstrate that individual condensates can serve as sensors to detect tyrosinase activity, with a limit of detection similar to that of synthetic fluorescent probes. This approach opens opportunities to utilize designer biomolecular condensates as diagnostic tools for various disorders involving abnormal enzymatic activity.
Topics: RNA; Melanins; Monophenol Monooxygenase; Proteins; Peptides; Organelles
PubMed: 37871222
DOI: 10.1073/pnas.2310569120 -
Molecules (Basel, Switzerland) Dec 2022Abnormal skin pigmentation commonly occurs during the wound healing process due to the overproduction of melanin. Chicken egg white (CEW) has long been used to improve...
Abnormal skin pigmentation commonly occurs during the wound healing process due to the overproduction of melanin. Chicken egg white (CEW) has long been used to improve skin health. Previous published works had found CEW proteins house bioactive peptides that inhibit tyrosinase, the key enzyme of melanogenesis. The current study aimed to evaluate the anti-pigmentation potential and mechanism of the CEW-derived peptide (GYSLGNWVCAAK) and hydrolysates (CEWH and CEWH), using a cell-based model. All of these peptide and hydrolysates inhibited intracellular tyrosinase activity and melanin level up to 45.39 ± 1.31 and 70.01 ± 1.00%, respectively. GYSLGNWVCAAK and CEWH reduced intracellular cAMP levels by 13.38 ± 3.65 and 14.55 ± 2.82%, respectively; however, CEWH did not affect cAMP level. Moreover, the hydrolysates downregulated the mRNA expression of melanogenesis-related genes, such as , , and , but GYSLGNWVCAAK only suppressed gene expression. Downregulation of the genes may lower the catalytic activities and/or affect the structural stability of TYR, TRP-1 and TRP-2; thus, impeding melanogenesis to cause an anti-pigmentation effect in the cell. Outcomes from the current study could serve as the starting point to understand the underlying complex, multifaceted melanogenesis regulatory mechanism at the cellular level.
Topics: Animals; Melanins; Monophenol Monooxygenase; Chickens; Skin Pigmentation; Egg White; Peptides
PubMed: 36615286
DOI: 10.3390/molecules28010092