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Journal of Translational Medicine Apr 2024Melanocytes are dendritic cells localized in skin, eyes, hair follicles, ears, heart and central nervous system. They are characterized by the presence of melanosomes... (Review)
Review
Melanocytes are dendritic cells localized in skin, eyes, hair follicles, ears, heart and central nervous system. They are characterized by the presence of melanosomes enriched in melanin which are responsible for skin, eye and hair pigmentation. They also have different functions in photoprotection, immunity and sound perception. Melanocyte dysfunction can cause pigmentary disorders, hearing and vision impairments or increased cancer susceptibility. This review focuses on the role of melanocytes in homeostasis and disease, before discussing their potential in regenerative medicine applications, such as for disease modeling, drug testing or therapy development using stem cell technologies, tissue engineering and extracellular vesicles.
Topics: Regenerative Medicine; Melanocytes; Pigmentation; Melanins; Hair Follicle
PubMed: 38589876
DOI: 10.1186/s12967-024-05113-x -
Biochimica Et Biophysica Acta.... Feb 2024Choroideremia (CHM) is a rare X-linked chorioretinal dystrophy affecting the photoreceptors, retinal pigment epithelium (RPE) and choroid, however, the involvement of...
Choroideremia (CHM) is a rare X-linked chorioretinal dystrophy affecting the photoreceptors, retinal pigment epithelium (RPE) and choroid, however, the involvement of the choroid in disease progression is not fully understood. CHM is caused by mutations in the CHM gene, encoding the ubiquitously expressed Rab escort protein 1 (REP1). REP1 plays an important role in intracellular trafficking of vesicles, including melanosomes. In this study, we examined the ultrastructure of the choroid in chm fish and Chm mouse models using transmission electron and confocal microscopy. Significant pigmentary disruptions were observed, with lack of melanosomes in the choroid of chm fish from 4 days post fertilisation (4dpf), and a reduction in choroidal blood vessel diameter and interstitial pillars suggesting a defect in vasculogenesis. Total melanin and expression of melanogenesis genes tyr, tryp1a, mitf, dct and pmel were also reduced from 4dpf. In Chm mice, choroidal melanosomes were significantly smaller at 1 month, with reduced eumelanin at 1 year. The choroid in CHM patients were also examined using spectral domain optical coherence tomography (SD-OCT) and OCT-angiography (OCT-A) and the area of preserved choriocapillaris (CC) was found to be smaller than that of overlying photoreceptors, suggesting that the choroid is degenerating at a faster rate. Histopathology of an enucleated eye from a 74-year-old CHM male patient revealed isolated areas of RPE but no associated underlying CC. Pigmentary disruptions in CHM animal models reveal an important role for REP1 in melanogenesis, and drugs that improve melanin production represent a potential novel therapeutic avenue.
Topics: Aged; Animals; Humans; Male; Mice; Adaptor Proteins, Signal Transducing; Choroid; Choroideremia; Melanins; Melanogenesis; Mice, Knockout
PubMed: 37989423
DOI: 10.1016/j.bbadis.2023.166963 -
Journal of Insect Physiology Jun 2024Water regulation is an important physiological challenge for insects due to their small body sizes and large surface area to volume ratios. Adaptations for decreasing...
Water regulation is an important physiological challenge for insects due to their small body sizes and large surface area to volume ratios. Adaptations for decreasing cuticular water loss, the largest avenue of loss, are especially important. The melanin desiccation hypothesis states that melanin molecules in the cuticle may help prevent water loss, thus offering protection from desiccation. This hypothesis has much empirical support in Drosophila species, but remains mostly untested in other taxa, including Lepidoptera. Because melanin has many other important functions in insects, its potential role in desiccation prevention is not always clear. In this study we investigated the role of melanin in desiccation prevention in the white-lined Sphinx moth, Hyles lineata (Lepidoptera, Sphingidae), which shows high plasticity in the degree of melanin pigmentation during the late larval instars. We took advantage of this plasticity and used density treatments to induce a wide range of cuticular melanization; solitary conditions induced low melanin pigmentation while crowded conditions induced high melanin pigmentation. We tested whether more melanic larvae from the crowded treatment were better protected from desiccation in three relevant responses: i) total water loss over a desiccation period, ii) change in hemolymph osmolality over a desiccation period, and iii) evaporation rate of water through the cuticle. We did not find support for the melanin desiccation hypothesis in this species. Although treatment influenced total water loss, this effect did not occur via degree of melanization. Interestingly, this implies that crowding, which was used to induce high melanin phenotypes, may have other physiological effects that influence water regulation. There were no differences between treatments in cuticular evaporative water loss or change in hemolymph osmolality. However, we conclude that osmolality may not sufficiently reflect water loss in this case. This study emphasizes the context dependency of melanin's role in desiccation prevention and the importance of considering how it may vary across taxa. In lepidopteran larvae that are constantly feeding phytophagous insects with soft cuticles, melanin may not be necessary for preventing cuticular water loss.
PubMed: 38936542
DOI: 10.1016/j.jinsphys.2024.104669 -
Biochemistry and Biophysics Reports Sep 2023Aberrant melanin overproduction can significantly impact an individual's appearance and cause mental and psychological distress. Current inhibitors of melanin production...
Aberrant melanin overproduction can significantly impact an individual's appearance and cause mental and psychological distress. Current inhibitors of melanin production exert harmful side effects due to inadequate selectivity; thus a need to develop more selective melanin synthesis inhibitors is necessary. Extracellular vesicles are important agents of intercellular signalling in prokaryotes and eukaryotes. Recently, plant-derived nanoparticles, similar to mammalian exosomes, have attracted attention for their use in health research. In this study, to investigate the potential of plant-derived exosome-like nanoparticles (ELNs) as inhibitors of melanin production, we used hot water to extract ELNs from the rhizome of (A-ELNs). The size of A-ENLs ranged from 34 to 401 nm and carried three microRNA: ath-miR166f, ath-miR162a-5p, and ath-miR162b-5p. These A-ENLs were applied to B16-F10 melanoma cells treated with α-melanocyte-stimulating hormone (α-MSH). After A-ELNs were taken up by B16-F10 cells, their melanin levels were significantly reduced. Furthermore, A-ELNs significantly reduced tyrosinase activity in B16-F10 cells and mRNA expression of microphthalmia-associated transcription factor (), tyrosinase, tyrosinase-related protein 1, and DOPA chrome tautomerase. These results suggest that A-ELN suppresses melanogenic enzymes expression by downregulating , thereby inhibiting melanin synthesis. Hence, A-ELN can be developed into a novel topical drug after additional studies and optimization.
PubMed: 37637942
DOI: 10.1016/j.bbrep.2023.101530 -
Frontiers in Microbiology 2023, a highly sought-after edible mushroom worldwide, is evaluated based on its cap color as an essential commercial property indicator. In the present study, the effects...
, a highly sought-after edible mushroom worldwide, is evaluated based on its cap color as an essential commercial property indicator. In the present study, the effects of blue light on cap pigmentation in , as well as the synthesis and structural characteristics of melanin pigments within the cap were examined. The results showed that an increase in the proportion of blue light within the lighting environment promoted melanin synthesis and melanization of the cap. Transmission and scanning electron microscopy revealed the localization of melanin within the mycelium and its ultrastructural characteristics. The UV-visible analysis demonstrated that melanin exhibited a maximum absorption peak at 220 nm and possessed high alkaline solubility as well as acid precipitability. The structural characteristics of melanin were analyzed using FTIR, NMR, HPLC, and elemental analysis, which confirmed the presence of eumelanin, pheomelanin, and allomelanin in both brown and black caps. Furthermore, blue light can stimulate the synthesis of both eumelanin and pheomelanin. The obtained results can serve as the foundation for comprehending the mechanism by which light regulates color formation in mushrooms.
PubMed: 37840742
DOI: 10.3389/fmicb.2023.1276457 -
Brain : a Journal of Neurology Apr 2024Degeneration of the noradrenergic system is now considered a pathological hallmark of Parkinson's disease, but little is known about its consequences in terms of...
Degeneration of the noradrenergic system is now considered a pathological hallmark of Parkinson's disease, but little is known about its consequences in terms of parkinsonian manifestations. Here, we evaluated two aspects of the noradrenergic system using multimodal in vivo imaging in patients with Parkinson's disease and healthy controls: the pigmented cell bodies of the locus coeruleus with neuromelanin sensitive MRI; and the density of α2-adrenergic receptors (ARs) with PET using 11C-yohimbine. Thirty patients with Parkinson's disease and 30 age- and sex-matched healthy control subjects were included. The characteristics of the patients' symptoms were assessed using the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Patients showed reduced neuromelanin signal intensity in the locus coeruleus compared with controls and diminished 11C-yohimbine binding in widespread cortical regions, including the motor cortex, as well as in the insula, thalamus and putamen. Clinically, locus coeruleus neuronal loss was correlated with motor (bradykinesia, motor fluctuations, tremor) and non-motor (fatigue, apathy, constipation) symptoms. A reduction of α2-AR availability in the thalamus was associated with tremor, while a reduction in the putamen, the insula and the superior temporal gyrus was associated with anxiety. These results highlight a multifaceted alteration of the noradrenergic system in Parkinson's disease since locus coeruleus and α2-AR degeneration were found to be partly uncoupled. These findings raise important issues about noradrenergic dysfunction that may encourage the search for new drugs targeting this system, including α2-ARs, for the treatment of Parkinson's disease.
Topics: Humans; Parkinson Disease; Tremor; Carbon Radioisotopes; Positron-Emission Tomography; Norepinephrine; Locus Coeruleus; Magnetic Resonance Imaging; Melanins
PubMed: 37787503
DOI: 10.1093/brain/awad338 -
Marine Biotechnology (New York, N.Y.) Aug 2023Melanogenesis is a multistep process to produce melanin for dark pigmentation in skin coloration. Previous studies in vertebrates demonstrated that cystine and tyrosine...
Melanogenesis is a multistep process to produce melanin for dark pigmentation in skin coloration. Previous studies in vertebrates demonstrated that cystine and tyrosine amino acids are involved in the melanin synthesis. However, very little is known about the melanogenesis in bivalve. In this study, cystine supplementation for 30 days significantly upregulated the expression of CgB-aat1, CgCbs and CgTyr and pheomelanin content in the Pacific oyster Crassostrea gigas. Transmission electron microscope (TEM) results revealed more melanosomes in the connective tissue and melanin granules were secreted in epithelium of mantle. In contrast, tyrosine supplementation had no clear effect on melanogenesis except the gene expression changes of CgB-aat1 and CgCbs. In addition, prolonged supplementation of cystine or tyrosine for 60 days had a negative impact on melanogenesis. Indeed, after 60 days, expression of most of the melanin synthesis-related genes under study was decreased, and melanin content was significantly reduced, indicating that cystine and tyrosine might inhibit production of eumelanin and pheomelanin, respectively. In addition, in vitro analysis using primary cell culture from mantle tissue indicated that incubation with cystine, tyrosine, or B-AAT1 polypeptide, CBS/TYR recombinant proteins induced the increase of CgB-aat1 and CgCbs expression in a dose-dependent manner, suggesting the presence of a regulatory network in response to cystine and tyrosine amino acids intakes in pheomelanin synthesis-related gene expression. Taken together, these data indicate that cystine-CgB-aat1-CgCbs-CgTyr axis is a potential regulator of the pheomelanin biosynthesis pathway, and thus plays an important role in the mantle pigmentation in C. gigas. This work provides a new clue for selective cultivation of oyster strains with specific shell colors in bivalve breeding.
Topics: Animals; Tyrosine; Melanins; Cystine; Crassostrea; Dietary Supplements
PubMed: 37369882
DOI: 10.1007/s10126-023-10223-6 -
The Journal of Investigative Dermatology Oct 2023cAMP signaling is a well-established regulator of melanin synthesis. Two distinct cAMP signaling pathways-the transmembrane adenylyl cyclase pathway, activated primarily...
cAMP signaling is a well-established regulator of melanin synthesis. Two distinct cAMP signaling pathways-the transmembrane adenylyl cyclase pathway, activated primarily by the MC1R, and the soluble adenylyl cyclase (sAC) pathway-affect melanin synthesis. The sAC pathway affects melanin synthesis by regulating melanosomal pH, and the MC1R pathway affects melanin synthesis by regulating gene expression and post-translational modifications. However, whether MC1R genotype affects melanosomal pH is poorly understood. We now report that loss of function MC1R does not affect melanosomal pH. Thus, sAC signaling appears to be the only cAMP signaling pathway that regulates melanosomal pH. We also addressed whether MC1R genotype affects sAC-dependent regulation of melanin synthesis. Although sAC loss of function in wild-type human melanocytes stimulates melanin synthesis, sAC loss of function has no effect on melanin synthesis in MC1R nonfunctional human and mouse melanocytes or skin and hair melanin in e/e mice. Interestingly, activation of transmembrane adenylyl cyclases, which increases epidermal eumelanin synthesis in e/e mice, leads to enhanced production of eumelanin in sAC-knockout mice relative to that in sAC wild-type mice. Thus, MC1R- and sAC-dependent cAMP signaling pathways define distinct mechanisms that regulate melanosomal pH and pigmentation.
Topics: Mice; Animals; Humans; Melanins; Adenylyl Cyclases; Receptor, Melanocortin, Type 1; Pigmentation; Melanocytes; Signal Transduction; Mice, Knockout; Hydrogen-Ion Concentration
PubMed: 37142186
DOI: 10.1016/j.jid.2023.04.011 -
Biochemical and Biophysical Research... Sep 2023This study investigated anti-melanogenesis effects of enzyme-treated caviar extract (CV) in murine melanoma B16F10 cells and SKH-1 hairless mice. To induce melanin...
This study investigated anti-melanogenesis effects of enzyme-treated caviar extract (CV) in murine melanoma B16F10 cells and SKH-1 hairless mice. To induce melanin production in vitro and in vivo studies, B16F10 cells were treated with 3-Isobutyl-1-methylxanthine (IBMX), and SKH-1 hairless mice were irradiated with UVB, respectively. The expression of melnogenesis-related factors and signaling molecules were analyzed by ELISA and western blotting. 50, 100 and 200 μg/mL of CV significantly decreased the melanin contents and the activities of tyrosinase, nitric oxide, glutathione, and cAMP, melanogenesis factor, in B16F10 cells treated IBMX. In addition, CV significantly suppressed the expression of melanogenesis proteins such as pPKA, pCREB, MITF, TRP-1and TRP-2. Similarly, results of oral administration of CV (20, 50 and 100 mg/kg) for 8 weeks in UVB-Induced SKH-1 hairless mice, the expression of melanogenesis-related factor tyrosinase, nitric oxide, and cAMP and protein expression of pPKA, pCREBa, MITF, TRP-1and TRP-2 was significantly reduced. In particular, 100 mg/kg of CV exhibited an excellent effect similar to control group. Therefore, we suggest the possibility of developing CV as a food supplement having skin whitening effects by ameliorating melanogenesis.
Topics: Melanoma, Experimental; Animals; Mice; Melanogenesis; Eggs; Mice, Hairless; Melanins; Ultraviolet Rays; Tissue Extracts; 1-Methyl-3-isobutylxanthine; Skin Lightening Preparations; Humans; Male
PubMed: 37364389
DOI: 10.1016/j.bbrc.2023.05.016 -
Experimental Cell Research Jan 2024The voltage-dependent anion channel 1 (VDAC1) forms an oligomeric structure on the mitochondrial outer membrane, which plays critical roles in many physiological...
The voltage-dependent anion channel 1 (VDAC1) forms an oligomeric structure on the mitochondrial outer membrane, which plays critical roles in many physiological processes. Research studies have demonstrated that the knockout of VDAC1 increases pigment content and up-regulates the expression of melanogenic genes. Due to its involvement in various physiological processes, the depletion of VDAC1 has significant detrimental effects on cellular functions and the inhibition of VDAC1 oligomerization has recently emerged as a promising strategy for the treatment of several diseases. In this study, we found that VDAC1 oligomerization inhibitors, VBIT-12 and NSC-15364, promote melanogenesis, dendrite formation and melanosome transport in human epidermal melanocytes (HEMCs). Mechanistically, treatment of HEMCs with an oligomerization inhibitor increased the level of cytoplasmic calcium ions, which activated calcium-calmodulin dependent protein kinase (CaMK) and led to the phosphorylation of CREB and the nuclear translocation of CREB-regulated transcription coactivators (CRTCs). Subsequently, CRTCs, p-CREB and CREB-binding protein (CBP) in the nucleus cooperatively recruit the transcription machinery to initiate the transcription of MITF thus promoting pigmentation. Importantly, our study also demonstrates that VDAC1 oligomerization inhibitors increase pigmentation in zebrafish and in human skin explants, highlighting their potential as a therapeutic strategy for skin pigmentation disorders.
Topics: Animals; Humans; Pigmentation Disorders; Voltage-Dependent Anion Channel 1; Calcium; Zebrafish; Melanocytes; Melanins; Pigmentation; Microphthalmia-Associated Transcription Factor
PubMed: 38070860
DOI: 10.1016/j.yexcr.2023.113874