-
Cells Dec 2022Selective autophagy controls cellular homeostasis by degrading unnecessary or damaged cellular components. Melanosomes are specialized organelles that regulate the...
Selective autophagy controls cellular homeostasis by degrading unnecessary or damaged cellular components. Melanosomes are specialized organelles that regulate the biogenesis, storage, and transport of melanin in melanocytes. However, the mechanisms underlying melanosomal autophagy, known as the melanophagy pathway, are poorly understood. To better understand the mechanism of melanophagy, we screened an endocrine-hormone chemical library and identified nalfurafine hydrochlorides, a κ-opioid receptor agonist, as a potent inducer of melanophagy. Treatment with nalfurafine hydrochloride increased autophagy and reduced melanin content in alpha-melanocyte-stimulating hormone (α-MSH)-treated cells. Furthermore, inhibition of autophagy blocked melanosomal degradation and reversed the nalfurafine hydrochloride-induced decrease in melanin content in α-MSH-treated cells. Consistently, treatment with other κ-opioid receptor agonists, such as MCOPPB or mianserin, inhibited excessive melanin production but induced autophagy in B16F1 cells. Furthermore, nalfurafine hydrochloride inhibited protein kinase A (PKA) activation, which was notably restored by forskolin, a PKA activator. Additionally, forskolin treatment further suppressed melanosomal degradation as well as the anti-pigmentation activity of nalfurafine hydrochloride in α-MSH-treated cells. Collectively, our data suggest that stimulation of κ-opioid receptors induces melanophagy by inhibiting PKA activation in α-MSH-treated B16F1 cells.
Topics: alpha-MSH; Colforsin; Melanins; Receptors, Opioid, kappa; Cyclic AMP-Dependent Protein Kinases; Animals; Mice
PubMed: 36611940
DOI: 10.3390/cells12010146 -
Cells Jun 2022Pigmentation is an important process in skin physiology and skin diseases and presumably also plays a role in Parkinson's disease (PD). In PD, alpha-Synuclein (aSyn) has...
Pigmentation is an important process in skin physiology and skin diseases and presumably also plays a role in Parkinson's disease (PD). In PD, alpha-Synuclein (aSyn) has been shown to be involved in the pigmentation of neurons. The presynaptic protein is intensively investigated for its pathological role in PD, but its physiological function remains unknown. We hypothesized that aSyn is both involved in melanocytic differentiation and melanosome trafficking processes. We detected a strong expression of aSyn in human epidermal melanocytes (NHEMs) and observed its regulation in melanocytic differentiation via the microphthalmia-associated transcription factor (MITF), a central regulator of differentiation. Moreover, we investigated its role in pigmentation by performing siRNA experiments but found no effect on the total melanin content. We discovered a localization of aSyn to melanosomes, and further analysis of aSyn knockdown revealed an important role in melanocytic morphology and a reduction in melanosome release. Additionally, we found a reduction of transferred melanosomes in co-culture experiments of melanocytes and keratinocytes but no complete inhibition of melanosome transmission. In summary, this study highlights a novel physiological role of aSyn in melanocytic morphology and its so far unknown function in the pigment secretion in melanocytes.
Topics: Humans; Keratinocytes; Melanins; Melanocytes; Melanosomes; alpha-Synuclein
PubMed: 35805172
DOI: 10.3390/cells11132087 -
Journal of Nanobiotechnology Nov 2022Currently, tumor treatments are characterized by intelligence, diversity and personalization, but the therapeutic reagents used are often limited in clinical efficacy... (Review)
Review
Currently, tumor treatments are characterized by intelligence, diversity and personalization, but the therapeutic reagents used are often limited in clinical efficacy due to problems with water solubility, targeting, stability and multidrug resistance. To remedy these shortcomings, the application of multifunctional nanotechnology in the biomedical field has been widely studied. Synthetic melanin nanoparticles (MNPs) surfaces which contain highly reactive chemical groups such as carboxyl, hydroxyl and amine groups, can be used as a reaction platform on which to graft different functional components. In addition, MNPs easily adhere to substrate surface, and serve as a secondary reaction platform to modify it. The multifunctionality and intrinsic biocompatibility make melanin-like nanoparticles promising as a multifunctional and powerful nanoplatform for oncological applications. This paper first reviews the preparation methods, polymerization mechanisms and physicochemical properties of melanin including natural melanin and chemically synthesized melanin to guide scholars in MNP-based design. Then, recent advances in MNPs especially synthetic polydopamine (PDA) melanin for various medical oncological applications are systematically and thoroughly described, mainly focusing on bioimaging, photothermal therapy (PTT), and drug delivery for tumor therapy. Finally, based on the investigated literature, the current challenges and future directions for clinical translation are reasonably discussed, focusing on the innovative design of MNPs and further elucidation of pharmacokinetics. This paper is a timely and comprehensive and detailed study of the progress of MNPs in tumor therapy, especially PTT, and provides ideas for the design of personalized and customizable oncology nanomedicines to address the heterogeneity of the tumor microenvironment.
Topics: Humans; Melanins; Photothermal Therapy; Nanoparticles; Nanomedicine; Neoplasms; Tumor Microenvironment
PubMed: 36402976
DOI: 10.1186/s12951-022-01698-x -
International Journal of Molecular... May 2023The melanin pigments eumelanin (EM) and pheomelanin (PM), which are dark brown to black and yellow to reddish-brown, respectively, are widely found among vertebrates.... (Review)
Review
The melanin pigments eumelanin (EM) and pheomelanin (PM), which are dark brown to black and yellow to reddish-brown, respectively, are widely found among vertebrates. They are produced in melanocytes in the epidermis, hair follicles, the choroid, the iris, the inner ear, and other tissues. The diversity of colors in animals is mainly caused by the quantity and quality of their melanin, such as by the ratios of EM versus PM. We have developed micro-analytical methods to simultaneously measure EM and PM and used these to study the biochemical and genetic fundamentals of pigmentation. The photoreactivity of melanin has become a major focus of research because of the postulated relevance of EM and PM for the risk of UVA-induced melanoma. Our biochemical methods have found application in many clinical studies on genetic conditions associated with alterations in pigmentation. Recently, besides chemical degradative methods, other methods have been developed for the characterization of melanin, and these are also discussed here.
Topics: Animals; Melanins; Melanocytes; Pigmentation; Epidermis; Melanoma
PubMed: 37176019
DOI: 10.3390/ijms24098305 -
Skin Research and Technology : Official... Aug 2023Melasma is an acquired skin problem. It characterises sun-exposed areas, particularly on the face, with irregular borders and bilateral distribution. With this study, we...
BACKGROUND
Melasma is an acquired skin problem. It characterises sun-exposed areas, particularly on the face, with irregular borders and bilateral distribution. With this study, we want to strengthen the scientific literature regarding the use of a 675-nm laser device for the treatment of women and men with facial melasma pigmentary and vascular symptoms.
MATERIALS AND METHODS
Eighteen patients were treated for facial melasma. A total of three sessions at 30-day intervals were performed with a 675-nm laser device. A five-point Global Aesthetic Improvement Scale was used to separately assess the improvement of the patient's skin 3 months after the last treatment (T1) compared to baseline (T0). The pain during treatment was measured using a Visual Analog Scale of 10 points. The non-ablative laser system used emits red light with a wavelength of 675 nm through a 13 × 13 mm scanning system.
RESULTS
At T , a consistent improvement in the pigmentary and vascular components was visible. This is always combined with a considerable reduction in vascular expression.
CONCLUSION
Our research shows that individuals with Fitzpatrick phototypes II to III can treat facial melasma with the 675-nm laser source system without risk. Due to its interaction with melanin, collagen and haemoglobin chromophores, as well as its excellent capacity to penetrate tissues with less heating, this system is promising in the treatment of pigmentary and vascular illnesses such as melasma. The great success of the technology we used came from the reduced levels of inflammation produced after the treatments and the low energy level implied.
Topics: Male; Humans; Female; Esthetics; Inflammation; Light; Melanins; Melanosis
PubMed: 37632189
DOI: 10.1111/srt.13434 -
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 -
International Journal of Molecular... Jun 2023Syringetin, an active compound present in red grapes, jambolan fruits, , and , is a dimethyl myricetin derivative which contains free hydroxyl groups at the C-2' and...
Syringetin, an active compound present in red grapes, jambolan fruits, , and , is a dimethyl myricetin derivative which contains free hydroxyl groups at the C-2' and C-4' positions in ring B. Recent studies have revealed that syringetin possesses multiple pharmacological properties, such as antitumor, hepatoprotective, antidiabetic, antioxidative, and cytoprotective activities. To date, there has been no attempt to test the action of syringetin on melanogenesis. In addition, the molecular mechanism for the melanogenic effects of syringetin remains largely unknown. In this study, we investigated the effect of syringetin on melanogenesis in a murine melanoma cell line from a C57BL/6J mouse, B16F10. Our results showed that syringetin markedly stimulated melanin production and tyrosinase activity in a concentration-dependent manner in B16F10 cells. We also found that syringetin increased MITF, tyrosinase, TRP-1, and TRP-2 protein expression. Moreover, syringetin inhibited ERK and PI3K/Akt phosphorylation by stimulating p38, JNK, PKA phosphorylation levels, subsequently stimulating MITF and TRP upregulation, resulting in the activation of melanin synthesis. Furthermore, we observed that syringetin activated phosphorylation of GSK3β and β-catenin and reduced the protein level of β-catenin, suggesting that syringetin stimulates melanogenesis through the GSK3β/β-catenin signal pathway. Finally, a primary skin irritation test was conducted on the upper backs of 31 healthy volunteers to determine the irritation or sensitization potential of syringetin for topical application. The results of the test indicated that syringetin did not cause any adverse effects on the skin. Taken together, our findings indicated that syringetin may be an effective pigmentation stimulator for use in cosmetics and in the medical treatment of hypopigmentation disorders.
Topics: Animals; Mice; Melanins; Monophenol Monooxygenase; beta Catenin; Glycogen Synthase Kinase 3 beta; Phosphatidylinositol 3-Kinases; Mice, Inbred C57BL; Cell Line, Tumor; Microphthalmia-Associated Transcription Factor; Melanoma, Experimental
PubMed: 37373110
DOI: 10.3390/ijms24129960 -
Cells Jun 2022Melanosomes are melanocyte-specific organelles that protect cells from ultraviolet (UV)-induced deoxyribonucleic acid damage through the production and accumulation of... (Review)
Review
Melanosomes are melanocyte-specific organelles that protect cells from ultraviolet (UV)-induced deoxyribonucleic acid damage through the production and accumulation of melanin and are transferred from melanocytes to keratinocytes. The relatively well-known process by which melanin is synthesized from melanocytes is known as melanogenesis. The relationship between melanogenesis and autophagy is attracting the attention of researchers because proteins associated with autophagy, such as WD repeat domain phosphoinositide-interacting protein 1, microtubule-associated protein 1 light chain 3, autophagy-related (ATG)7, ATG4, beclin-1, and UV-radiation resistance-associated gene, contribute to the melanogenesis signaling pathway. Additionally, there are reports that some compounds used as whitening cosmetics materials induce skin depigmentation through autophagy. Thus, the possibility that autophagy is involved in the removal of melanin has been suggested. To date, however, there is a lack of data on melanosome autophagy and its underlying mechanism. This review highlights the importance of autophagy in melanin homeostasis by providing an overview of melanogenesis, autophagy, the autophagy machinery involved in melanogenesis, and natural compounds that induce autophagy-mediated depigmentation.
Topics: Autophagy; Homeostasis; Melanins; Melanocytes; Melanosomes
PubMed: 35805169
DOI: 10.3390/cells11132085 -
Journal of Biomedical Optics Oct 2023Evaluation of biological chromophore levels is useful for detection of various skin diseases, including cancer, monitoring of health status and tissue metabolism, and...
SIGNIFICANCE
Evaluation of biological chromophore levels is useful for detection of various skin diseases, including cancer, monitoring of health status and tissue metabolism, and assessment of clinical and physiological vascular functions. Clinically, it is useful to assess multiple different chromophores with a single technique or instrument.
AIM
To investigate the possibility of estimating the concentration of four chromophores, bilirubin, oxygenated hemoglobin, deoxygenated hemoglobin, and melanin from diffuse reflectance spectra in the visible region.
APPROACH
A new diffuse reflectance spectroscopic method based on the multiple regression analysis aided by Monte Carlo simulations for light transport was developed to quantify bilirubin, oxygenated hemoglobin, deoxygenated hemoglobin, and melanin. Three different experimental animal models were used to induce hyperbilirubinemia, hypoxemia, and melanogenesis in rats.
RESULTS
The estimated bilirubin concentration increased after ligation of the bile duct and reached around at 50 h after the onset of ligation, which corresponds to the reference value of bilirubin measured by a commercially available transcutaneous bilirubin meter. The concentration of oxygenated hemoglobin and that of deoxygenated hemoglobin decreased and increased, respectively, as the fraction of inspired oxygen decreased. Consequently, the tissue oxygen saturation dramatically decreased. The time course of melanin concentration after depilation of skin on the back of rats was indicative of the supply of melanosomes produced by melanocytes of hair follicles to the growing hair shaft.
CONCLUSIONS
The results of our study showed that the proposed method is capable of the evaluation of percutaneous bilirubin level, skin hemodynamics, and melanogenesis in rats, and that it has potential as a tool for the diagnosis and management of hyperbilirubinemia, hypoxemia, and pigmented skin lesions.
Topics: Rats; Animals; Melanins; Bilirubin; Spectrum Analysis; Skin; Hypoxia; Hemoglobins; Oxyhemoglobins; Hyperbilirubinemia
PubMed: 37915398
DOI: 10.1117/1.JBO.28.10.107001 -
Frontiers of Neurology and Neuroscience 2021During the last decade, optogenetic-based circuit mapping has become one of the most common approaches to systems neuroscience, and amassing studies have expanded our... (Review)
Review
During the last decade, optogenetic-based circuit mapping has become one of the most common approaches to systems neuroscience, and amassing studies have expanded our understanding of brain structures causally involved in the regulation of sleep-wake cycles. Recent imaging technologies enable the functional mapping of cellular activity, from population down to single-cell resolution, across a broad repertoire of behaviors and physiological processes, including sleep-wake states. This chapter summarizes experimental evidence implicating hypocretins/orexins, melanin-concentrating hormone, and inhibitory neurons from the lateral hypothalamus (LH) in forming an intricate network involved in regulating sleep and metabolism, including feeding behaviors. It further confirms the dual sleep-metabolic functions of LH cells, and sheds light on a possible mechanism underlying brain plasticity during sleep and metabolic disorders.
Topics: Animals; Feeding Behavior; Humans; Hypothalamic Area, Lateral; Hypothalamic Hormones; Melanins; Nerve Net; Neurons; Orexins; Pituitary Hormones; Sleep
PubMed: 34052816
DOI: 10.1159/000514966