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Nucleic Acids Research Oct 2023Melanin protects skin cells from ultraviolet radiation-induced DNA damage. However, intermediates of eumelanin are highly reactive quinones that are potentially...
Melanin protects skin cells from ultraviolet radiation-induced DNA damage. However, intermediates of eumelanin are highly reactive quinones that are potentially genotoxic. In this study, we systematically investigate the effect of sustained elevation of melanogenesis and map the consequent cellular repair response of melanocytes. Pigmentation increases γH2AX foci, DNA abasic sites, causes replication stress and invokes translesion polymerase Polκ in primary human melanocytes, as well as mouse melanoma cells. Confirming the causal link, CRISPR-based genetic ablation of tyrosinase results in depigmented cells with low Polκ levels. During pigmentation, Polκ activates replication stress response and keeps a check on uncontrolled proliferation of cells harboring melanin-damaged DNA. The mutational landscape observed in human melanoma could in part explain the error-prone bypass of DNA lesions by Polκ, whose absence would lead to genome instability. Thereby, translesion polymerase Polκ is a critical response of pigmenting melanocytes to combat melanin-induced DNA alterations. Our study illuminates the dark side of melanin and identifies (eu)melanogenesis as a key missing link between tanning response and mutagenesis, mediated via the necessary evil translesion polymerase, Polκ.
Topics: Animals; Humans; Mice; DNA Damage; DNA Repair; DNA-Directed DNA Polymerase; Melanins; Melanocytes; Melanoma; Pigmentation; Ultraviolet Rays
PubMed: 37697436
DOI: 10.1093/nar/gkad704 -
Journal of Nanobiotechnology Sep 2023Excessive and prolonged ultraviolet radiation (UVR) exposure causes photodamage, photoaging, and photocarcinogenesis in human skin. Therefore, safe and effective sun...
Excessive and prolonged ultraviolet radiation (UVR) exposure causes photodamage, photoaging, and photocarcinogenesis in human skin. Therefore, safe and effective sun protection is one of the most fundamental requirements. Living organisms tend to evolve various natural photoprotective mechanisms to avoid photodamage. Among them, melanin is the main functional component of the photoprotective system of human skin. Polydopamine (PDA) is synthesized as a mimic of natural melanin, however, its photoprotective efficiency and mechanism in protecting against skin damage and photoaging remain unclear. In this study, the novel sunscreen products based on melanin-inspired PDA nanoparticles (NPs) are rationally designed and prepared. We validate that PDA NPs sunscreen exhibits superior effects on photoprotection, which is achieved by the obstruction of epidermal hyperplasia, protection of the skin barrier, and resolution of inflammation. In addition, we find that PDA NPs are efficiently intake by keratinocytes, exhibiting robust ROS scavenging and DNA protection ability with minimal cytotoxicity. Intriguingly, PDA sunscreen has an influence on maintaining homeostasis of the dermis, displaying an anti-photoaging property. Taken together, the biocompatibility and full photoprotective properties of PDA sunscreen display superior performance to those of commercial sunscreen. This work provides new insights into the development of a melanin-mimicking material for sunscreens.
Topics: Humans; Sunscreening Agents; Ultraviolet Rays; Antioxidants; Melanins; Skin; Anti-Inflammatory Agents
PubMed: 37775761
DOI: 10.1186/s12951-023-02107-7 -
Advances in Skin & Wound Care Oct 2023To examine the effectiveness of the ColorMeter DSM III (ColorMeter; Cortex Technology) at grouping individuals by skin tone and measuring erythema/skin discoloration...
OBJECTIVE
To examine the effectiveness of the ColorMeter DSM III (ColorMeter; Cortex Technology) at grouping individuals by skin tone and measuring erythema/skin discoloration after erythema induction across skin tones.
METHODS
This pre/post experimental study induced erythema on a convenience sample of 61 healthy adults. Skin tone at baseline was measured using the ColorMeter, Munsell Soil Color Chart 5YR (Munsell), and Pantone SkinTone Guide (Pantone) and compared with the Eumelanin Human Skin Colour Scale (Eumelanin Scale) groupings. Erythema and melanin values on the arm immediately and after recovery time were compared with baseline values. Melanin was measured at five body regions on the face and arm.
RESULTS
Participants were predominantly women (64% [n = 39] women, 36% [n = 22] men) and young (mean, 28.8 ± 14.3 years); 5% (n = 3) were Hispanic, 26% (n = 16) Asian, 29% (n = 18) Black, 38% (n = 23) White, and 7% (n = 4) identified with more than one race. ColorMeter lightness (L*) and melanin measures were strongly correlated with both Munsell and Pantone values. Munsell skin tone groups were not aligned with Eumelanin Scale groupings. Most participants were in the Eumelanin intermediate-low group, and this changed depending on which body location melanin value was used. The change in erythema from baseline did not differ significantly across skin tone groups at the ulnar head, but on the forearm at the delayed time point, significant differences existed between light and both medium and dark skin tone groups (P = .001; 95% CI, 0.04-0.37).
CONCLUSIONS
The ColorMeter provides an effective objective measure of skin tone and erythema/discoloration across various skin tones and may improve on current standards for detection. The proposed Eumelanin Scale-Modified provides additional sensitivity for persons with medium skin tones.
Topics: Male; Female; Humans; Skin Pigmentation; Melanins; Erythema; Upper Extremity; Technology
PubMed: 37729162
DOI: 10.1097/ASW.0000000000000043 -
The Analyst Jul 2023Melanin nanoparticles (NPs) have important biological functions including photoprotection and colouration, and artificial melanin-like NPs are relevant for catalysis,...
Melanin nanoparticles (NPs) have important biological functions including photoprotection and colouration, and artificial melanin-like NPs are relevant for catalysis, drug delivery, diagnosis and therapy. Despite their importance, the optical properties of single melanin NPs have not been measured. We combine quantitative differential interference contrast (qDIC) and extinction microscopy to characterise the optical properties of single NPs, both naturally sourced from cuttlefish ink, as well as synthetic NPs using polydopamine (PDA) and L-3,4-dihydroxyphenylalanine (L-DOPA). Combining qDIC with extinction, we determine the absorption index of individual NPs. We find that on average the natural melanin NPs have a higher absorption index than the artificial melanin NPs. From the analysis of the polarisation-dependent NP extinction, the NP aspect ratio is determined, with mean values at 405 nm wavelength in agreement with transmission electron microscopy. At longer wavelengths, we observe an additional optical anisotropy which is attributed to dichroism by structural ordering of the melanin. Our quantitative analysis yields a dichroism of 2-10% of the absorption index, increasing with wavelength from 455 nm to 660 nm for L-DOPA and PDA. Such an in-depth quantification of the optical properties of single melanin NPs is important for the design and future application of these ubiquitous bionanomaterials.
Topics: Melanins; Levodopa; Nanoparticles
PubMed: 37382583
DOI: 10.1039/d3an00654a -
International Journal of Molecular... Oct 2023Melatonin (-acetyl-5-methoxytryptamine, MEL), its kynurenic (-acetyl--formyl-5-methoxykynurenine, AFMK) and indolic derivatives (6-hydroxymelatonin, 6(OH)MEL and...
Melatonin (-acetyl-5-methoxytryptamine, MEL), its kynurenic (-acetyl--formyl-5-methoxykynurenine, AFMK) and indolic derivatives (6-hydroxymelatonin, 6(OH)MEL and 5-methoxytryptamine, 5-MT) are endogenously produced in human epidermis. Melatonin, produced by the pineal gland, brain and peripheral organs, displays a diversity of physiological functions including anti-inflammatory, immunomodulatory, and anti-tumor capacities. Herein, we assessed their regulatory effect on melanogenesis using amelanotic (A375, Sk-Mel-28) and highly pigmented (MNT-1, melanotic) human melanoma cell lines. We discovered that subjected compounds decrease the downstream pathway of melanin synthesis by causing a significant drop of cyclic adenosine monophosphate (cAMP) level, the microphthalmia-associated transcription factor (MITF) and resultant collapse of tyrosinase (TYR) activity, and melanin content comparatively to -phenylthiourea (PTU, a positive control). We observed a reduction in pigment in melanosomes visualized by the transmission electron microscopy. Finally, we assessed the role of G-protein-coupled seven-transmembrane-domain receptors. Obtained results revealed that nonselective MT1 and MT2 receptor antagonist (luzindole) or selective MT2 receptor antagonist (4-P-PDOT) did not affect dysregulation of the melanin pathway indicating a receptor-independent mechanism. Our findings, together with the current state of the art, provide a convenient experimental model to study the complex relationship between metabolites of melatonin and the control of pigmentation serving as a future and rationale strategy for targeted therapies of melanoma-affected patients.
Topics: Humans; Melatonin; Melanins; 5-Methoxytryptamine; Receptor, Melatonin, MT2; Melanoma; Monophenol Monooxygenase
PubMed: 37834395
DOI: 10.3390/ijms241914947 -
Biomedicine & Pharmacotherapy =... Sep 2023Panax ginseng, also known as Korean ginseng, is a traditional remedy widely used in Asian countries. Its major active compounds are ginsenosides, specifically...
Panax ginseng, also known as Korean ginseng, is a traditional remedy widely used in Asian countries. Its major active compounds are ginsenosides, specifically triterpenoid saponins. Among them, one notable ginsenoside called Re has shown various biological effects, including anti-cancer and anti-inflammatory properties. However, the potential beneficial effects of Re on melanogenesis and skin cancer remain poorly understood. To investigate this, we conducted a comprehensive study using biochemical assays, cell-based models, a zebrafish pigment formation model, and a tumor xenograft model. Our results revealed that Re effectively inhibited melanin biosynthesis in a dose-dependent manner by competitively inhibiting the activity of tyrosinase, an enzyme involved in melanin production. Moreover, Re significantly reduced the mRNA expression levels of microphthalmia-associated transcription factor (MITF), a key regulator of melanin biosynthesis and melanoma growth. Furthermore, Re decreased the protein expression of MITF and its target genes, including tyrosinase, TRP-1, and TRP-2, through a partially ubiquitin-dependent proteasomal degradation mechanism, mediated by the AKT and ERK signaling pathways. These findings indicate that Re exerts its hypopigmentary effects by directly inhibiting tyrosinase activity and suppressing its expression via MITF. Additionally, Re demonstrated inhibitory effects on skin melanoma growth and induced tumor vascular normalization in our in vivo experiments. This study represents the first evidence of Re-mediated inhibition of melanogenesis and skin melanoma, shedding light on the underlying mechanisms. These promising preclinical findings warrant further investigation to determine the suitability of Re as a natural agent for treating hyperpigmentation disorders and skin cancer.
Topics: Animals; Humans; Ginsenosides; Monophenol Monooxygenase; Melanins; Microphthalmia-Associated Transcription Factor; Zebrafish; Cell Line, Tumor; Melanoma; Skin Neoplasms; Melanoma, Experimental; Melanoma, Cutaneous Malignant
PubMed: 37393867
DOI: 10.1016/j.biopha.2023.115037 -
Journal of Oleo Science 2024Hair is important to our appearance as well as to protect our heads. Human hair mainly consists of proteins (80-85%), melanin pigments (0-5%), water (10-13%), and lipids... (Review)
Review
Hair is important to our appearance as well as to protect our heads. Human hair mainly consists of proteins (80-85%), melanin pigments (0-5%), water (10-13%), and lipids (1-6%). The physicochemical properties of hair have been studied for over 100 years. However, they are not yet thoroughly understood. In this review, recent progress and the latest findings are summarized from the following three perspectives: structural characteristics, delivery and distribution of active ingredients, and hair as a template. The structural characteristics of hair have been mainly investigated by microscopic and/or spectroscopic techniques such as atomic force microscopy integrated with infrared spectroscopy (AFM-IR) and rheological measurements. The distribution of active ingredients has been generally evaluated through techniques such as nanoscale secondary ion mass spectrometry (NanoSIMS). And finally, attempts to explore the potential of hair to be used as a substrate for flexible device fabrication will be introduced.
Topics: Hair; Humans; Microscopy, Atomic Force; Melanins; Chemical Phenomena; Spectrometry, Mass, Secondary Ion; Rheology; Spectrophotometry, Infrared; Lipids; Water; Proteins
PubMed: 38825536
DOI: 10.5650/jos.ess23203 -
Proceedings of the National Academy of... Aug 2023Hypothalamic inflammation reduces appetite and body weight during inflammatory diseases, while promoting weight gain when induced by high-fat diet (HFD). How...
Hypothalamic inflammation reduces appetite and body weight during inflammatory diseases, while promoting weight gain when induced by high-fat diet (HFD). How hypothalamic inflammation can induce opposite energy balance outcomes remains unclear. We found that prostaglandin E (PGE), a key hypothalamic inflammatory mediator of sickness, also mediates diet-induced obesity (DIO) by activating appetite-promoting melanin-concentrating hormone (MCH) neurons in the hypothalamus in rats and mice. The effect of PGE on MCH neurons is excitatory at low concentrations while inhibitory at high concentrations, indicating that these neurons can bidirectionally respond to varying levels of inflammation. During prolonged HFD, endogenous PGE depolarizes MCH neurons through an EP2 receptor-mediated inhibition of the electrogenic Na/K-ATPase. Disrupting this mechanism by genetic deletion of EP2 receptors on MCH neurons is protective against DIO and liver steatosis in male and female mice. Thus, an inflammatory mediator can directly stimulate appetite-promoting neurons to exacerbate DIO and fatty liver.
Topics: Mice; Rats; Male; Female; Animals; Obesity; Melanins; Hypothalamus; Inflammation; Fatty Liver; Diet, High-Fat; Neurons; Inflammation Mediators; Prostaglandins
PubMed: 37467285
DOI: 10.1073/pnas.2302809120 -
Journal of Fish Biology Sep 2023Isolated cases of skin pigment disorders, including leucism, in sharks and rays have been reported for multiple species. Nonetheless, the morphological basis behind...
Isolated cases of skin pigment disorders, including leucism, in sharks and rays have been reported for multiple species. Nonetheless, the morphological basis behind these chromatic anomalies has not been examined histologically. In this study, the authors quantified and compared the presence of melanin in multiple tissue samples of leucistic and fully pigmented blacktip sharks Carcharhinus limbatus. The authors' results support lack of melanin to be responsible for leucistic colouration. The histological differences responsible were evaluated.
Topics: Animals; Sharks; Melanins
PubMed: 37167015
DOI: 10.1111/jfb.15431 -
Brain : a Journal of Neurology Feb 2024Disruptions to dopamine and noradrenergic neurotransmission are noted in several neurodegenerative and psychiatric disorders. Neuromelanin-sensitive (NM)-MRI offers a... (Review)
Review
Disruptions to dopamine and noradrenergic neurotransmission are noted in several neurodegenerative and psychiatric disorders. Neuromelanin-sensitive (NM)-MRI offers a non-invasive approach to visualize and quantify the structural and functional integrity of the substantia nigra and locus coeruleus. This method may aid in the diagnosis and quantification of longitudinal changes of disease and could provide a stratification tool for predicting treatment success of pharmacological interventions targeting the dopaminergic and noradrenergic systems. Given the growing clinical interest in NM-MRI, understanding the contrast mechanisms that generate this signal is crucial for appropriate interpretation of NM-MRI outcomes and for the continued development of quantitative MRI biomarkers that assess disease severity and progression. To date, most studies associate NM-MRI measurements to the content of the neuromelanin pigment and/or density of neuromelanin-containing neurons, while recent studies suggest that the main source of the NM-MRI contrast is not the presence of neuromelanin but the high-water content in the dopaminergic and noradrenergic neurons. In this review, we consider the biological and physical basis for the NM-MRI contrast and discuss a wide range of interpretations of NM-MRI. We describe different acquisition and image processing approaches and discuss how these methods could be improved and standardized to facilitate large-scale multisite studies and translation into clinical use. We review the potential clinical applications in neurological and psychiatric disorders and the promise of NM-MRI as a biomarker of disease, and finally, we discuss the current limitations of NM-MRI that need to be addressed before this technique can be utilized as a biomarker and translated into clinical practice and offer suggestions for future research.
Topics: Humans; Catecholamines; Magnetic Resonance Imaging; Substantia Nigra; Melanins; Dopamine; Biomarkers
PubMed: 37669320
DOI: 10.1093/brain/awad300