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International Journal of Molecular... Oct 2020Melanin is an important phenolic skin pigment found throughout the animal kingdom. Tyrosine and its hydroxylated product dopa provide the starting material for melanin...
Melanin is an important phenolic skin pigment found throughout the animal kingdom. Tyrosine and its hydroxylated product dopa provide the starting material for melanin biosynthesis in all animals. Through a set of well-established reactions, they are converted to 5,6-dihydroxyindole (DHI) and DHI-2-carboxylic acid (DHICA). Oxidative polymerization of these two indoles produces the brown to black eumelanin pigment. The steps associated with these transformations are complicated by the extreme instability of the starting materials and the transient and highly reactive nature of the intermediates. We have used mass spectral studies to explore the nonenzymatic mechanism of oxidative transformation of DHI in water. Our results indicate the facile production of not only dimeric and trimeric products but also higher oligomeric forms of DHI upon exposure to air in solution, even under nonenzymatic conditions. Such instantaneous polymerization of DHI avoids toxicity to self-matter and ensures the much-needed deposition of melanin at (a) the wound site and (b) the infection site in arthropods. The rapid deposition of DHI melanin is advantageous for arthropods given their open circulatory system; the process limits blood loss during wounding and prevents the spread of parasites by encapsulating them in melanin, limiting the damage.
Topics: Animals; Carboxylic Acids; Dihydroxyphenylalanine; Immunity, Innate; Indoles; Melanins; Monophenol Monooxygenase; Oxidative Stress; Polymers
PubMed: 33023030
DOI: 10.3390/ijms21197321 -
International Journal of Molecular... Jun 2023Melanin is a complex natural pigment that is widely present in fungi. The mushroom has a variety of pharmacological effects. The active substances of have been...
Melanin is a complex natural pigment that is widely present in fungi. The mushroom has a variety of pharmacological effects. The active substances of have been extensively studied, but few studies have focused on the melanin. In this study, the production of melanin was increased by adding light or oxidative stress, namely, reactive oxygen species (ROS) or reactive nitrogen species (RNS), during liquid fermentation. Subsequently, the structure of the purified melanin was characterized using elemental analysis, ultraviolet-visible absorption spectrum, Fourier transform infrared (FTIR), electron paramagnetic resonance (EPR), and pyrolysis gas chromatography and mass spectrometry (Py-GCMS). Studies have shown that melanin is composed of C (50.59), H (6.18), O (33.90), N (8.19), and S (1.20), with maximum absorbance at 237 nm and typical melanin structures such as benzene, indole, and pyrrole. Additionally, the various biological activities of melanin have been discovered; it can chelate heavy metals and shows a strong ultraviolet-blocking ability. Moreover, melanin can reduce the levels of intracellular reactive oxygen species and counteract the oxidative damage of HO to cells. These results can help us to develop applications of melanin in radiation resistance, heavy metal pollution remediation, and antioxidant use.
Topics: Cordyceps; Melanins; Reactive Oxygen Species; Hydrogen Peroxide; Agaricales
PubMed: 37373428
DOI: 10.3390/ijms241210282 -
Transactions of the Royal Society of... Apr 2021Eumycetoma is a fungal infection characterised by the formation of black grains by causative agents. The melanin biosynthetic pathways used by the most common causative...
BACKGROUND
Eumycetoma is a fungal infection characterised by the formation of black grains by causative agents. The melanin biosynthetic pathways used by the most common causative agents of black-grain mycetoma are unknown and unravelling them could identify potential new therapeutic targets.
METHOD
Melanin biosynthetic pathways in the causative fungi were identified by the use of specific melanin inhibitors.
RESULTS
In Trematosphaeria grisea and Falciformispora tompkinsii, 1,8-dihydroxynaphthalene (DHN)-melanin synthesis was inhibited, while DHN-, 3,4-dihydroxyphenylalanine (DOPA)- and pyo-melanin were inhibited in Medicopsis romeroi and Falciformispora senegalensis.
CONCLUSION
Our data suggest that Me. romeroi and F. senegalensis synthesise DHN-, DOPA- and pyo-melanin, while T. grisea and F. tompkinsii only synthesise DHN-melanin.
Topics: Ascomycota; Melanins; Mycetoma
PubMed: 33463687
DOI: 10.1093/trstmh/traa168 -
Inflammation Apr 2024Vitiligo is a skin disease characterized by selective loss of melanocytes, which seriously affects the appearance and causes great psychological stress to patients. In...
Vitiligo is a skin disease characterized by selective loss of melanocytes, which seriously affects the appearance and causes great psychological stress to patients. In this study, we performed a comprehensive analysis of two vitiligo microarray datasets from the GEO database using bioinformatics tools to identify 297 up-regulated mRNAs and 186 down-regulated mRNAs, revealing important roles for pathways related to melanin synthesis, tyrosine metabolism, and inflammatory factors, such as "PPAR signaling pathway", "tyrosine metabolism", "nonalcoholic fatty liver disease (NAFLD) pathway", "melanogenesis", and "IL-17 signaling pathway". Combining the Search Tool for Interacting Chemicals (STITCH) database 5.0 and the drug-gene interaction database 3.0 (DGIdb), we identified that the PPAR-γ agonist rosiglitazone may promote melanin synthesis via EDNRB. Next, we investigated the mechanism of rosiglitazone and PPAR-γ pathway in promoting melanin production. Consistent with the results of bioinformatics analysis, the expression levels of PPAR-γ, EDNRB, and TYR were significantly reduced in human non-segmental vitiligo skin along with the reduction of MITF, a key gene for epidermal melanogenesis. Meanwhile, rosiglitazone increased melanin synthesis capacity in melanocytes and zebrafish by activating PPAR-γ and upregulating TYR, TYRP-1, and TYRP-2. Conversely, treatment of melanocytes with the PPAR-γ antagonist GW resulted in inhibition of melanin synthesis and expression of melanin-related factors. At the same time, simultaneous treatment of rosiglitazone with GW reversed the inhibitory effect of GW on melanin synthesis. In this study, we identified that rosiglitazone, an important insulin sensitizer, promotes melanin synthesis in melanocytes by increasing PPAR-γ activity and upregulating the expression levels of EDNRB and TYR. These findings may provide new ideas for exploring the pathogenesis and potential therapeutic targets of non-segmental vitiligo.
Topics: Vitiligo; Humans; PPAR gamma; Rosiglitazone; Melanocytes; Animals; Melanins; Zebrafish; Receptor, Endothelin B; Computational Biology; Signal Transduction
PubMed: 38159176
DOI: 10.1007/s10753-023-01937-9 -
Environmental Microbiology Reports Aug 2022As human activity in space continues to increase, understanding how biological assets respond to spaceflight conditions is becoming more important. Spaceflight...
As human activity in space continues to increase, understanding how biological assets respond to spaceflight conditions is becoming more important. Spaceflight conditions include exposure to ionizing radiation, microgravity, spacecraft vibrations and hypervelocity; all of which can affect the viability of biological organisms. Previous studies have shown that melanin-producing fungi are capable of surviving the vacuum of space and Mars-simulated conditions in Low Earth Orbit. This survival has been associated in part with the protective effects of melanin, but a comparison of fungal viability in the presence or absence of melanin following spaceflight has never been tested. In this study, we evaluated the protective effects of melanin by comparing the viability of melanized and non-melanized clones of Cryptococcus neoformans yeasts following a roundtrip to the International Space Station. Yeast colonies were placed inside two MixStix silicone tubes; one stayed on Earth and the other was transported inside for 29 days before returning to Earth. Post-flight analysis based on colony-forming unit numbers shows that melanized yeast viability was 50% higher than non-melanized yeasts, while no difference was observed between the Earth-bound control samples. The results suggest that fungal melanin could increase the lifespan of biological assets in space.
Topics: Cryptococcus neoformans; Humans; Melanins; Saccharomyces cerevisiae; Space Flight
PubMed: 35852045
DOI: 10.1111/1758-2229.13078 -
Current Protocols Jan 2021Cryptococcus neoformans is an opportunistic fungal pathogen primarily targeting immunosuppressed populations in both resource-rich and resource-limited nations....
Cryptococcus neoformans is an opportunistic fungal pathogen primarily targeting immunosuppressed populations in both resource-rich and resource-limited nations. Successful treatment is limited to a few antifungals that have become compromised by cryptococcal resistance, leading to intensive research seeking new drug candidates. Two distinguishing hallmarks of this species are the ability to develop a polysaccharide capsule and melanization of the fungal cells. These also act as virulence factors, protecting this pathogen in the host as well as in the environment. Here we describe two classic methods to document capsule and melanin. Although initially described and documented several decades ago, these methods remain relevant in spite of the advent of more sophisticated methodology, due in part to their simplicity and cost efficiency. © 2021 Wiley Periodicals LLC. Basic Protocol 1: Capsule visualization by India ink counterstaining Basic Protocol 2: Assessment of melanin on solid media Alternative Protocol: Quantification of melanin production in liquid medium.
Topics: Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Documentation; Humans; Melanins
PubMed: 33484487
DOI: 10.1002/cpz1.27 -
Immunity, Inflammation and Disease Jan 2022Imiquimod plays an important role in the management of condyloma and premalignant lesions. Successively, an increase of hypopigmented lesions following imiquimod...
INTRODUCTION
Imiquimod plays an important role in the management of condyloma and premalignant lesions. Successively, an increase of hypopigmented lesions following imiquimod application has been reported. However, the mechanisms of imiquimod on melanocytes remain unclear. This study was designed to assess the effect of Imiquimod on the functions of melanocytes in vitro.
METHODS
Primary cultured melanocytes were isolated from normal control skin tissue. After incubation with imiquimod for 48 h in vitro, cell viability was analyzed by cell counting kit-8 assay. Apoptosis was detected using the Annexin V-fluorescein-5-isothiocyanate flow cytometry assay. Melanin content and tyrosinase activity in melanocytes were measured by colorimetric method and the modified dopachrome method. The production of inflammatory cytokine interleukin 8 (IL-8), IL-6, and soluble ICAM-1 (soluble Intercellular Adhesion Molecule-1[sICAM-1]) in melanocytes were measured by enzyme-linked immunosorbent assay (ELISA). Toll-like receptor 7 (TLR7), toll-like receptor 9 (TLR9) protein, and autophagy-related proteins microtubule-associated protein 1A/1B-light chain 3 (LC3-II), p62, mechanistic target of rapamycin (mTOR), and Atg5 were assessed using western blot analysis.
RESULTS
Imiquimod significantly inhibited the activity of tyrosinase activity and decreased melanin content in melanocytes and significantly increased apoptosis and IL-6, IL-8, and sICAM-1 production in melanocytes. Moreover, the expression of TLR7 and TLR9 proteins were significantly increased, and the expression of mTOR, p62 protein were markedly decreased, but the expression of LC3II/I and Atg5 protein were significantly increased in melanocytes after incubating with imiquimod.
CONCLUSIONS
This study shows that imiquimod directly inhibits melanogenesis and increases melanocyte apoptosis rates. These effects combined with the upregulation of TLR7 and TLR9 together with increased autophagy activity and inflammatory cytokines production, might be the main reasons leading to hypopigmented lesions after imiquimod application.
Topics: Apoptosis; Humans; Imiquimod; Melanins; Melanocytes; Vitiligo
PubMed: 34614305
DOI: 10.1002/iid3.543 -
Journal of Industrial Microbiology &... Jul 2022Pyomelanin is a brown-black phenolic polymer and results from the oxidation of homogentisic acid (HGA) in the L-tyrosine pathway. As part of the research for natural and... (Review)
Review
Pyomelanin is a brown-black phenolic polymer and results from the oxidation of homogentisic acid (HGA) in the L-tyrosine pathway. As part of the research for natural and active ingredients issued from realistic bioprocesses, this work re-evaluates the HGA pigment and makes an updated inventory of its syntheses, microbial pathways, and properties, with tracks and recent advances for its large-scale production. The mechanism of the HGA polymerization is also well documented. In alkaptonuria, pyomelanin formation leads to connective tissue damage and arthritis, most probably due to the ROS issued from HGA oxidation. While UV radiation on human melanin may generate degradation products, pyomelanin is not photodegradable, is hyperthermostable, and has other properties better than L-Dopa melanin. This review aims to raise awareness about the potential of this pigment for various applications, not only for skin coloring and protection but also for other cells, materials, and as a promising (semi)conductor for bioelectronics and energy.
Topics: Homogentisic Acid; Humans; Melanins; Pigmentation; Tyrosine
PubMed: 35482661
DOI: 10.1093/jimb/kuac013 -
Current Biology : CB Sep 2020At oceanic depths >200 m, there is little ambient sunlight, but bioluminescent organisms provide another light source that can reveal animals to visual predators and...
At oceanic depths >200 m, there is little ambient sunlight, but bioluminescent organisms provide another light source that can reveal animals to visual predators and prey [1-4]. Transparency and mirrored surfaces-common camouflage strategies under the diffuse solar illumination of shallower waters-are conspicuous when illuminated by directed bioluminescent sources due to reflection from the body surface [5, 6]. Pigmentation allows animals to absorb light from bioluminescent sources, rendering them visually undetectable against the dark background of the deep sea [5]. We present evidence suggesting pressure to reduce reflected bioluminescence led to the evolution of ultra-black skin (reflectance <0.5%) in 16 species of deep-sea fishes across seven distantly related orders. Histological data suggest this low reflectance is mediated by a continuous layer of densely packed melanosomes in the exterior-most layer of the dermis [7, 8] and that this layer lacks the unpigmented gaps between pigment cells found in other darkly colored fishes [9-13]. Using finite-difference, time-domain modeling and comparisons with melanosomes found in other ectothermic vertebrates [11, 13-21], we find the melanosomes making up the layer in these ultra-black species are optimized in size and shape to minimize reflectance. Low reflectance results from melanosomes scattering light within the layer, increasing the optical path length and therefore light absorption by the melanin. By reducing reflectance, ultra-black fish can reduce the sighting distance of visual predators more than 6-fold compared to fish with 2% reflectance. This biological example of efficient light absorption via a simple architecture of strongly absorbing and highly scattering particles may inspire new ultra-black materials.
Topics: Adaptation, Physiological; Animals; Biological Mimicry; Color; Fishes; Melanins; Melanosomes; Oceans and Seas; Skin Pigmentation
PubMed: 32679102
DOI: 10.1016/j.cub.2020.06.044 -
International Journal of Molecular... Aug 2017Optoacoustic imaging emerged in early 1990s as a new biomedical imaging technology that generates images by illuminating tissues with short laser pulses and detecting... (Review)
Review
Optoacoustic imaging emerged in early 1990s as a new biomedical imaging technology that generates images by illuminating tissues with short laser pulses and detecting resulting ultrasound waves. This technique takes advantage of the spectroscopic approach to molecular imaging, and delivers high-resolution images in the depth of tissue. Resolution of the optoacoustic imaging is scalable, so that biomedical systems from cellular organelles to large organs can be visualized and, more importantly, characterized based on their optical absorption coefficient, which is proportional to the concentration of absorbing chromophores. Optoacoustic imaging was shown to be useful in both preclinical research using small animal models and in clinical applications. Applications in the field of molecular imaging offer abundant opportunities for the development of highly specific and effective contrast agents for quantitative optoacoustic imaging. Recent efforts are being made in the direction of nontoxic biodegradable contrast agents (such as nanoparticles made of melanin) that are potentially applicable in clinical optoacoustic imaging. In order to increase the efficiency and specificity of contrast agents and probes, they need to be made smart and capable of controlled accumulation in the target cells. This review was written in recognition of the potential breakthroughs in medical optoacoustic imaging that can be enabled by efficient and nontoxic melanin-based optoacoustic contrast agents.
Topics: Animals; Contrast Media; Diagnostic Imaging; Humans; Melanins; Molecular Imaging; Molecular Probes; Multimodal Imaging; Neoplasms; Photoacoustic Techniques; Theranostic Nanomedicine
PubMed: 28783106
DOI: 10.3390/ijms18081719