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Cancers Nov 2023A common feature of Parkinson's disease (PD) and melanoma is their starting points being based on cells capable of converting tyrosine into melanin. Melanocytes produce... (Review)
Review
A common feature of Parkinson's disease (PD) and melanoma is their starting points being based on cells capable of converting tyrosine into melanin. Melanocytes produce two types of melanin: eumelanin and pheomelanin. These dyes are designed to protect epidermal cells from the harmful effects of UV radiation. Neurones of the substantia nigra, which degenerate during PD, produce neuromelanin, the physiological role of which is not fully explained. This article discusses the potential role of melanins in the pathogenesis of both diseases. Melanins, due to their ability to accumulate toxic substances, may become their sources over time. The use of glutathione for the synthesis of pheomelanins and neuromelanins may reduce the antioxidant capacity of cells, leading to an excessive synthesis of free radicals. This study also tested the hypothesis that certain drugs used in the treatment of PD (L-DOPA, MAO-B and COMT inhibitors, and amantadine), aimed at increasing dopamine concentration, could potentially contribute to the development of melanoma. The role and properties of melanins should continue to be researched. Whether excessive melanin synthesis or its accumulation in the extracellular space may be factors initiating the development of diseases remains an open question.
PubMed: 38067245
DOI: 10.3390/cancers15235541 -
Archives of Microbiology Aug 2023Melanin is an amorphous polymer made of heterogeneous functional groups synthesized by diverse organisms including fungi, bacteria, animals, and plants. It was widely... (Review)
Review
Melanin is an amorphous polymer made of heterogeneous functional groups synthesized by diverse organisms including fungi, bacteria, animals, and plants. It was widely acknowledged for its biological processes and its key role in the protection of organisms from environmental stress. Recently, melanin clutches attention in the field of nanobiotechnology, drug delivery, organic semiconductors and bioelectronics, environmental bioremediation, photoprotection, etc., Furthermore, melanin from natural sources like microbial community shows antimicrobial, fighting cancer, radical scavenging, cosmeceuticals, and many therapeutic areas as well. Though the multipotentiality nature of melanin has been put forth, real-world applications still flag fall behind, which might be anticipated to the inadequate and high price essence of natural melanin. However, current bioprocess technologies have paved for the large-scale or industrial production of microbial melanin, which could help in the replacement of synthetic melanin. Thus, this review emphasizes the various sources for melanin, i.e., types-based on its pathways and its chemical structures, functional efficiency, physical properties, and conventional and modern methods of both extraction and characterization. Moreover, an outlook on how it works in the field of medicine, bioremediation, and other related areas provides perspectives on the complete exploitation of melanin in practical applications of medicine and the environment.
Topics: Animals; Melanins; Biopolymers; Anti-Infective Agents; Biodegradation, Environmental; Bacteria
PubMed: 37580645
DOI: 10.1007/s00203-023-03642-5 -
Molecular Biology Reports Jul 2023Melanosomes are lysosome-related organelles that contain melanogenic factors and synthesize melanin as they mature. FYVE finger-containing phosphoinositide kinase...
BACKGROUND
Melanosomes are lysosome-related organelles that contain melanogenic factors and synthesize melanin as they mature. FYVE finger-containing phosphoinositide kinase (PIKfyve) regulates late endosome and lysosome morphology, vesicle trafficking, and autophagy. In melanocytes, PIKfyve inhibition has been reported to induce hypopigmentation due to impairments in the metabolism of early-stage melanosomes.
METHODS AND RESULTS
Here, we report a new type of melanosome metabolism: post-PIKfyve inhibition, which was found during the characterization of the endosome/lysosome fluoroprobe GIF-2250. In B16F10 mouse melanoma cells, GIF-2250 highlighted vesicles positive for lysosomal-associated membrane protein 1 (lysosome marker) and other endosome/lysosome markers (CD63 and Rab7/9). When cells were continuously treated with PIKfyve inhibitors, intracellular vacuoles formed, while GIF-2250 fluorescence signals diminished and were diffusely distributed in the vacuoles. After removal of the PIKfyve inhibitors, the GIF-2250 signal intensity was restored, and some GIF-2250-positive vesicles wrapped the melanosomes, which spun at high speed. In addition, intermittent PIKfyve inhibition caused melanin diffusion in the vacuoles and possible leakage into the cytoplasmic compartments, and melanosome degradation was detected by a transmission electron microscope. Melanosome degradation was accompanied by decreased levels of melanin synthesis enzymes and increased levels of the autophagosome maker LC3BII, which is also associated with early melanosomes. However, the protein levels of p62, which is degraded during autophagy, were increased, suggesting an impairment in autophagy flux during intermittent PIKfyve inhibition. Moreover, the autophagy inhibitor 3-methyladenine does not affect these protein levels, suggesting that the melanosome degradation by the intermittent inhibition of PIKfyve is not mediated by canonical autophagy.
CONCLUSIONS
In conclusion, disturbance of PIKfyve activity induces melanosome degradation in a canonical autophagy-independent manner.
Topics: Animals; Mice; 1-Phosphatidylinositol 4-Kinase; Melanins; Melanocytes; Melanoma; Melanosomes
PubMed: 37248430
DOI: 10.1007/s11033-023-08536-9 -
Journal of Dermatological Science Nov 2023Advanced glycation end products (AGEs) promote melanogenesis through activating NLRP3 inflammasome in fibroblasts. Although A20 has been highlighted to inhibit NLRP3...
BACKGROUND
Advanced glycation end products (AGEs) promote melanogenesis through activating NLRP3 inflammasome in fibroblasts. Although A20 has been highlighted to inhibit NLRP3 inflammasome activation, its roles and mechanisms remain elusive in photoaging-associated pigmentation.
OBJECTIVES
To determine the significance of fibroblast A20 in AGEs-induced NLRP3 inflammasome activation and pigmentation.
METHODS
The correlation between A20 and AGEs or melanin was studied in sun-exposed skin and lesions of melasma and solar lentigo. We then investigated A20 level in AGEs-treated fibroblast and the effect of fibroblast A20 overexpression or knockdown on AGEs-BSA-induced NLRP3 inflammasome activation and pigmentation, respectively. Finally, the severity of NLRP3 inflammasome activation and pigmentation was evaluated after mice were injected intradermally with A20-overexpression adeno-associated virus and AGEs-BSA.
RESULTS
Dermal A20 expression was decreased and exhibited negative correlation with either dermal AGEs deposition or epidermal melanin level in sun-exposed skin and pigmentary lesions. Moreover, both AGEs-BSA and AGEs-collagen robustly decreased A20 expression via binding to RAGE in fibroblasts. Further, A20 overexpression or depletion significantly decreased or augmented AGEs-BSA-induced activation of NF-κB pathway and NLRP3 inflammasome and IL-18 production and secretion in fibroblasts, respectively. Importantly, fibroblast A20 potently repressed AGEs-BSA-stimulated melanin content,tyrosinase activity,and expression of microphthalmia-associated transcription factor and tyrosinase in melanocytes. Particularly, fibroblast A20 significantly abrogated AGEs-BSA-promoted melanogenesis in ex vivo skin and mouse models. Additionally, fibroblast A20 inhibited AGEs-BSA-activated MAPKs in melanocytes and the epidermis of ex vivo skin.
CONCLUSIONS
Fibroblast A20 suppresses AGEs-stimulate melanogenesis in photoaging-associated hyperpigmentation disorders by inhibiting NLRP3 inflammasome activation.
Topics: Humans; Animals; Mice; Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein; Signal Transduction; Glycation End Products, Advanced; Melanins; Monophenol Monooxygenase; Fibroblasts
PubMed: 37741724
DOI: 10.1016/j.jdermsci.2023.09.002 -
Investigative Ophthalmology & Visual... Nov 2023The purpose of this study was to demonstrate the utility of polarization-diversity optical coherence tomography (PD-OCT), a noninvasive imaging technique with...
PURPOSE
The purpose of this study was to demonstrate the utility of polarization-diversity optical coherence tomography (PD-OCT), a noninvasive imaging technique with melanin-specific contrast, in the quantitative and qualitative assessment of choroidal nevi.
METHODS
Nevi were imaged with a custom-built 55-degree field-of-view (FOV) 400 kHz PD-OCT system. Imaging features on PD-OCT were compared to those on fundus photography, auto-fluorescence, ultrasound, and non-PD-OCT images. Lesions were manually segmented for size measurement and metrics for objective assessment of melanin distributions were calculated, including degree of polarization uniformity (DOPU), attenuation coefficient, and melanin occupancy rate (MOR).
RESULTS
We imaged 17 patients (mean age = 69.5 years, range = 37-90) with 11 pigmented, 3 non-pigmented, and 3 mixed pigmentation nevi. Nevi with full margin acquisition had an average longest basal diameter of 5.1 mm (range = 2.99-8.72 mm) and average height of 0.72 mm (range = 0.37 mm-2.09 mm). PD-OCT provided clear contrast of choroidal melanin content, distribution, and delineation of nevus margins for melanotic nevi. Pigmented nevi were found to have lower DOPU, higher attenuation coefficient, and higher MOR than non-pigmented lesions. Melanin content on PD-OCT was consistent with pigmentation on fundus in 15 of 17 nevi (88%).
CONCLUSIONS
PD-OCT allows objective assessment of choroidal nevi melanin content and distribution. In addition, melanin-specific contrast by PD-OCT enables clear nevus margin delineation and may improve serial growth surveillance. Further investigation is needed to determine the clinical significance and prognostic value of melanin characterization by PD-OCT in the evaluation of choroidal nevi.
Topics: Humans; Adult; Middle Aged; Aged; Aged, 80 and over; Tomography, Optical Coherence; Melanins; Nevus, Pigmented; Nevus; Choroid Neoplasms; Skin Neoplasms
PubMed: 37930688
DOI: 10.1167/iovs.64.14.6 -
Nanoscale Dec 2023Melanin-inspired nanomaterials offer unique photophysical, electronic and radical scavenging properties that are widely explored for health and environmental...
Melanin-inspired nanomaterials offer unique photophysical, electronic and radical scavenging properties that are widely explored for health and environmental preservation, or energy conversion and storage. The incorporation of functional melanin building blocks in more complex nanostructures or surfaces is typically achieved a bottom-up approach starting from a molecular precursor, in most cases dopamine. Here we demonstrate that indeed, the oxidative polymerization of dopamine, for the synthesis of melanin-like polydopamine (PDA), leads to the simultaneous formation of more than one nanosized species with different compositions, morphologies and properties. In particular, a low-density polymeric structure and dense nanoparticles () are simultaneously formed. The two populations could be separated and analyzed in real time using a chromatographic technique free of any stationary phase (flow field fractionation, FFF). The results following the synthesis of melanin-like PDA showed that the are formed only during the first 6 hours as a result of a supramolecular self-assembly-driven polymerization, while the formation of the polymer continues for about 36 hours. The two populations were also separated and characterized using TEM, UV-vis absorption spectroscopy, fluorescence and light scattering spectroscopy, DLS, FTIR, ζ-potential measurements, gel electrophoresis and pH titrations. Interestingly, very different properties between the two populations were observed: in particular the polymer contains a higher number of catechol units (8 mmol g -OH) with respect to the (1 mmol g -OH) and presents a much higher antioxidant activity. The attenuation of light by is more efficient than that by the polymer especially in the Vis-NIR region. Moreover, while the scatter light with an efficiency up to 27% they are not fluorescent, and the polymer does not scatter light but shows an excitation wavelength-dependent fluorescence typical of multi-fluorophoric uncoupled systems.
Topics: Melanins; Biomimetics; Dopamine; Spectrum Analysis; Polymers
PubMed: 38059484
DOI: 10.1039/d3nr04696f -
Biochimica Et Biophysica Acta. Reviews... Nov 2023The skin containing melanin pigment acts as a protective barrier and counteracts the UVR and other environmental stressors to maintain or restore disrupted cutaneous... (Review)
Review
The skin containing melanin pigment acts as a protective barrier and counteracts the UVR and other environmental stressors to maintain or restore disrupted cutaneous homeostasis. The production of melanin pigment is dependent on tyrosine levels. L-tyrosine and L-dihydroxyphenylalanine (L-DOPA) can serve both as a substrates and intermediates of melanin synthetic pathway and as inducers and positive regulators of melanogenesis. The biosynthesis of melanin is stimulated upon exposure to UVR, which can also stimulate local production of hormonal factors, which can stimulate melanoma development by altering the chemical properties of eu- and pheomelanin. The process of melanogenesis can be altered by several pathways. One involves activation of POMC, with the production of POMC peptides including MSH and ACTH, which increase intracellular cAMP levels, which activates the MITF, and helps to stimulate tyrosinase (TYR) expression and activity. Defects in OCA1 to 4 affects melanogenic activity via posttranslational modifications resulting in proteasomal degradation and reducing pigmentation. Further, altering, the MITF factor, helps to regulate the expression of MRGE in melanoma, and helps to increase the TYR glycosylation in ER. CRH stimulates POMC peptides that regulate melanogenesis and also by itself can stimulate melanogenesis. The POMC, P53, ACTH, MSH, MC1R, MITF, and 6-BH4 are found to be important regulators for pigmentation. Melanogenesis can affect melanoma behaviour and inhibit immune responses. Therefore, we reviewed natural products that would alter melanin production. Our special focus was on targeting melanin synthesis and TYR enzyme activity to inhibit melanogenesis as an adjuvant therapy of melanotic melanoma. Furthermore, this review also outlines the current updated pharmacological studies targeting the TYR enzyme from natural sources and its consequential effects on melanin production.
Topics: Humans; Melanins; Melanoma; Monophenol Monooxygenase; Pro-Opiomelanocortin; Cell Line, Tumor; Tyrosine; Enzyme Inhibitors; Adrenocorticotropic Hormone
PubMed: 37657683
DOI: 10.1016/j.bbcan.2023.188968 -
BMC Complementary Medicine and Therapies Sep 2023We reported a gastric anti-ulcerogenic effect of the Nigella sativa (L.)-derived herbal melanin (HM) using rat models. However, the molecular mechanisms underlying this...
We reported a gastric anti-ulcerogenic effect of the Nigella sativa (L.)-derived herbal melanin (HM) using rat models. However, the molecular mechanisms underlying this HM gastroprotective effect remain unknown. Cyclooxygenase-2 (COX-2)-catalyzed prostaglandin E2 (PGE2) and toll-like receptor 4 (TLR4)-mediated interleukin-6 (IL-6) production and secretion play major roles in gastric mucosal protection. In the current study, the human gastric carcinoma epithelial cell line AGS was used as a model to investigate the effect of HM on TLR4, COX-2, glycoprotein mucin 4 protein and gene expression using immuno-cyto-fluorescence staining, Western blot technology, and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Gastroprotective markers PGE2 and IL-6 production and secretion were also assessed using an enzyme-linked immunosorbent assay (ELISA). Bacterial lipopolysaccharides (LPS), well-known inducers of TLR4, COX-2, PGE2 and IL-6 expression, were used as a positive control. We showed that HM upregulated its main receptor TLR4 gene and protein expression in AGS cells. HM increased, in a dose- and time-dependent manner, the secretion of PGE2 and the expression of COX-2 mRNA and protein, which was detected in the nucleus, cytoplasm and predominantly at the intercellular junctions of the AGS cells. In addition, HM enhanced IL-6 production and secretion, and upregulated the mucin 4 gene expression, the hallmarks of gastroprotection. To check whether HM-induced PGE2 and IL-6 through TLR4 signaling and COX-2 generated, AGS cells were pre-treated with a TLR4 signaling inhibitor TAK242 and the COX-2 inhibitor NS-398. A loss of the stimulatory effects of HM on COX-2, PGE2 and IL-6 production and secretion was observed in TAK242 and NS-398-pre-treated AGS cells, confirming the role of TLR4 signaling and COX-2 generated in the HM gastroprotective effects. In conclusion, our results showed that HM enhances TLR4/COX-2-mediated secretion of gastroprotective markers PGE2 and IL-6, and upregulates mucin 4 gene expression in the human gastric epithelial cell line AGS, which may contribute to the promising beneficial gastroprotective effect of HM for human gastric prevention and treatment.
Topics: Humans; Animals; Rats; Stomach Neoplasms; Melanins; Cyclooxygenase 2; Dinoprostone; Toll-Like Receptor 4; Interleukin-6; Mucin-4
PubMed: 37658354
DOI: 10.1186/s12906-023-04124-3 -
International Journal of Molecular... Aug 2023Melanin produced by melanocytes protects our skin against ultraviolet (UV) radiation-induced cell damage and oxidative stress. Melanin overproduction by hyperactivated...
Melanin produced by melanocytes protects our skin against ultraviolet (UV) radiation-induced cell damage and oxidative stress. Melanin overproduction by hyperactivated melanocytes is the direct cause of skin hyperpigmentary disorders, such as freckles and melasma. Exploring natural whitening agents without the concern of toxicity has been highly desired. In this study, we focused on a strain, ZJ1, isolated from a Chinese centenarian, and we evaluated the anti-melanogenic activity of the distinctive extracts of ZJ1. Our results demonstrated that whole lysate (WL) and bacterial lysate (BL) of ZJ1 ferments efficiently reduce α-melanocyte-stimulating hormone (α-MSH)-induced melanin production in B16-F10 cells as well as the melanin content in zebrafish embryos. BL and WL downregulate melanogenesis-related gene expression and indirectly inhibit intracellular tyrosinase activity. Furthermore, they both showed antioxidant activity in a menadione-induced zebrafish embryo model. Our results suggest that ZJ1 fermentation lysates have application potential as therapeutic reagents for hyperpigmentary disorders and whitening agents for cosmetics.
Topics: Animals; Humans; Antioxidants; Bifidobacterium longum; Bleaching Agents; Centenarians; East Asian People; Hyperpigmentation; Melanins; Zebrafish; Aged, 80 and over
PubMed: 37628988
DOI: 10.3390/ijms241612810 -
The Journal of Biological Chemistry Aug 2023Recent advancements in the treatment of melanoma are encouraging, but there remains a need to identify additional therapeutic targets. We identify a role for microsomal...
Recent advancements in the treatment of melanoma are encouraging, but there remains a need to identify additional therapeutic targets. We identify a role for microsomal glutathione transferase 1 (MGST1) in biosynthetic pathways for melanin and as a determinant of tumor progression. Knockdown (KD) of MGST1 depleted midline-localized, pigmented melanocytes in zebrafish embryos, while in both mouse and human melanoma cells, loss of MGST1 resulted in a catalytically dependent, quantitative, and linear depigmentation, associated with diminished conversion of L-dopa to dopachrome (eumelanin precursor). Melanin, especially eumelanin, has antioxidant properties, and MGST1 KD melanoma cells are under higher oxidative stress, with increased reactive oxygen species, decreased antioxidant capacities, reduced energy metabolism and ATP production, and lower proliferation rates in 3D culture. In mice, when compared to nontarget control, Mgst1 KD B16 cells had less melanin, more active CD8 T cell infiltration, slower growing tumors, and enhanced animal survival. Thus, MGST1 is an integral enzyme in melanin synthesis and its inhibition adversely influences tumor growth.
Topics: Animals; Humans; Mice; Glutathione Transferase; Melanins; Melanoma; Zebrafish; Oxidation-Reduction; Mice, Inbred C57BL; Cell Line, Tumor; Cell Proliferation
PubMed: 37321450
DOI: 10.1016/j.jbc.2023.104920