Exogenous Ochronosis by Hydroquinone is not caused by Inhibition of Homogentisate Dioxygenase but potentially by Tyrosinase-catalyzed Metabolism of Hydroquinone.

Background: Hydroquinone (HQ) is widely used for its hypopigmenting effects in treating hyperpigmentation disorders. However, its topical application has been linked to adverse effects, notably exogenous ochronosis (EO), raising concerns about its safety and mechanisms of action.

Objective: This study aims to elucidate the metabolic pathway of HQ in human melanocytes and clarify the role of tyrosinase in the development of EO.

Alteration of Hair Melanin in Patients With Mowat-Wilson Syndrome: The Role of the ZEB2 Gene in Regulating Melanogenesis Through SLC45A2.

Mowat-Wilson syndrome (MOWS) is a congenital disease characterized by intellectual disability, delayed motor development, characteristic facial features, epilepsy, and a wide spectrum of neurocristopathies. MOWS is caused by de novo heterozygous loss-of-function mutations or deletions in the zinc finger E-box-binding homeobox2 (ZEB2) gene, which is a multifunctional regulator of neuronal development and cancer progression/metastasis through epithelial-to-mesenchymal transition. We recognized that patients with MOWS have brown to red hair.

Photoreactive Properties of Melanin Obtained from Human Induced Pluripotent Stem Cell-Derived Melanocytes.

Although melanin is viewed as a natural sunscreen that protects pigmented cells against the adverse effects of solar radiation, recent studies have demonstrated that, under certain conditions, the pigment can actually contribute to light-induced oxidative damage of the cells. However, the main issue with such studies is finding natural pigments without photooxidative modifications. Recently, melanin obtained from melanocytes, generated from human induced pluripotent stem cells (hiPSC-Mel), was suggested as a promising source of the pigment without significant photooxidation.

A Cell-Based Evaluation of the Tyrosinase-Mediated Metabolic Activation of Leukoderma-Inducing Phenols, II: The Depletion of Augments the Cytotoxic Effect Evoked by Tyrosinase in Melanogenic Cells.

Chemical leukoderma is a disorder induced by chemicals such as rhododendrol and monobenzone. These compounds possess a -substituted phenol moiety and undergo oxidation into highly reactive and toxic -quinone metabolites by tyrosinase. This metabolic activation plays a critical role in the development of leukoderma through the production of damage to melanocytes and immunological responses.

Sperm Size Decreases With Increasing Pheomelanin Pigmentation but Not With the Amount of Glutathione in the Barn Swallow.

Pigment-based coloration is prevalent in animals, but its expression greatly varies across species, populations, and even among individuals in the same populations. Some animals are highly pigmented and thus have conspicuous coloration, whereas others are modestly pigmented and thus have drab coloration. A possible explanation for the variety in pigmentation is a resource-based tradeoff, in which resources invested in pigmentation are unavailable for other functional traits, and thus animals that need to invest in the latter have limited resources to invest in pigmentation.

Pterostilbene, a Dimethyl Derivative of Resveratrol, Exerts Cytotoxic Effects on Melanin-Producing Cells through Metabolic Activation by Tyrosinase.

Pterostilbene (PTS), which is abundant in blueberries, is a dimethyl derivative of the natural polyphenol resveratrol (RES). Several plant species, including peanuts and grapes, also produce PTS. Although RES has a wide range of health benefits, including anti-cancer properties, PTS has a robust pharmacological profile that includes a better intestinal absorption and an increased hepatic stability compared to RES.

The effect of oxidative degradation of Dopa-melanin on its basic physicochemical properties and photoreactivity.

Melanin, particularly eumelanin, is commonly viewed as an efficient antioxidant and photoprotective pigment. Nonetheless, the ability of melanin to photogenerate reactive oxygen species and sensitize the formation of cyclobutane pyrimidine dimers may contribute to melanin-dependent phototoxicity. The phototoxic potential of melanin depends on a variety of factors, including molecular composition, redox state, and degree of aggregation.

2-Mercaptonicotinoyl glycine, a new potent melanogenesis inhibitor, exhibits a unique mode of action while preserving melanocyte integrity.

Research on new ingredients that can prevent excessive melanin production in the skin while considering efficacy, safety but also environmental impact is of great importance to significantly improve the profile of existing actives on the market and avoid undesirable side effects. Here, the discovery of an innovative technology for the management of hyperpigmentation is described. High-throughput screening tests on a wide chemical diversity of molecules and in silico predictive methodologies were essential to design an original thiopyridinone backbone and select 2-mercaptonicotinoyl glycine (2-MNG) as exhibiting the most favorable balance between the impact on water footprint, skin penetration potential and performance.

Melanin-based plumage coloration and melanin content in organs in the barn owl.

Although the evolutionary ecology of melanin pigments and melanin-based coloration has been studied in great details, particularly in birds, little is known about the function of melanin stored inside the body. In the barn owl , in which individuals vary in the degree of reddish pheomelanin-based coloration and in the size of black eumelanic feather spots, we measured the concentration in melanin pigments in seven organs. The eyes had by far the most melanin then the skin, pectoral muscle, heart, liver, trachea, and uropygial gland.

Eumelanin Detection in Melanized Focal Changes but Not in Red Focal Changes on Atlantic Salmon () Fillets.

Superficial discolored spots on Atlantic salmon () fillets are a serious quality problem for commercial seafood farming. Previous reports have proposed that the black spots (called melanized focal changes (MFCs)) may be melanin, but no convincing evidence has been reported. In this study, we performed chemical characterization of MFCs and of red pigment (called red focal changes (RFCs)) from salmon fillets using alkaline hydrogen peroxide oxidation and hydroiodic acid hydrolysis.

Cytoglobin functions as a redox regulator of melanogenesis in normal epidermal melanocytes.

Epidermal melanocytes are continuously exposed to sunlight-induced reactive oxygen species (ROS) and oxidative stress generated during the synthesis of melanin. Therefore, they have developed mechanisms that maintain normal redox homeostasis. Cytoglobin (CYGB), a ubiquitously expressed intracellular iron hexacoordinated globin, exhibits antioxidant activity and regulates the redox state of mammalian cells through its activities as peroxidase and nitric oxide (NO) dioxygenase.

Taphonomic experiments reveal authentic molecular signals for fossil melanins and verify preservation of phaeomelanin in fossils.

Melanin pigments play a critical role in physiological processes and shaping animal behaviour. Fossil melanin is a unique resource for understanding the functional evolution of melanin but the impact of fossilisation on molecular signatures for eumelanin and, especially, phaeomelanin is not fully understood. Here we present a model for the chemical taphonomy of fossil eumelanin and phaeomelanin based on thermal maturation experiments using feathers from extant birds.

Recent Advances in Characterization of Melanin Pigments in Biological Samples.

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.

Distinct cAMP Signaling Microdomains Differentially Regulate Melanosomal pH and Pigmentation.

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.

A Sulfur Containing Melanogenesis Substrate, -Pr-4--CAP as a Potential Source for Selective Chemoimmunotherapy of Malignant Melanoma.

-propionyl-4--cysteaminylphenol (-Pr-4--CAP) is a substrate for tyrosinase, which is a melanin biosynthesis enzyme and has been shown to be selectively incorporated into melanoma cells. It was found to cause selective cytotoxicity against melanocytes and melanoma cells after selective incorporation, resulting in the induction of anti-melanoma immunity. However, the underlying mechanisms for the induction of anti-melanoma immunity remain unclear.

The role of tyrosine hydroxylase as a key player in neuromelanin synthesis and the association of neuromelanin with Parkinson's disease.

The dark pigment neuromelanin (NM) is abundant in cell bodies of dopamine (DA) neurons in the substantia nigra (SN) and norepinephrine (NE) neurons in the locus coeruleus (LC) in the human brain. During the progression of Parkinson's disease (PD), together with the degeneration of the respective catecholamine (CA) neurons, the NM levels in the SN and LC markedly decrease. However, questions remain among others on how NM is associated with PD and how it is synthesized.

Multiphoton FLIM Analyses of Native and UVA-Modified Synthetic Melanins.

To better understand the impact of solar light exposure on human skin, the chemical characterization of native melanins and their structural photo-modifications is of central interest. As the methods used today are invasive, we investigated the possibility of using multiphoton fluorescence lifetime (FLIM) imaging, along with phasor and bi-exponential fitting analyses, as a non-invasive alternative method for the chemical analysis of native and UVA-exposed melanins. We demonstrated that multiphoton FLIM allows the discrimination between native DHI, DHICA, Dopa eumelanins, pheomelanin, and mixed eu-/pheo-melanin polymers.

DOPA pheomelanin is increased in nigral neuromelanin of Parkinson's disease.

Neuromelanin (NM) in dopaminergic neurons of human substantia nigra (SN) has a melanic component that consists of pheomelanin and eumelanin moieties and has been proposed as a key factor contributing to dopaminergic neuron vulnerability in Parkinson's disease (PD). While eumelanin is considered as an antioxidant, pheomelanin and related oxidative stress are associated with compromised drug and metal ion binding and melanoma risk. Using postmortem SN from patients with PD or Alzheimer's disease (AD) and unaffected controls, we identified increased L-3,4-dihydroxyphenylalanine (DOPA) pheomelanin and increased ratios of dopamine (DA) pheomelanin markers to DA in PD SN compared to controls.

A cell-based evaluation of human tyrosinase-mediated metabolic activation of leukoderma-inducing phenolic compounds.

Background: Chemical leukoderma is a skin depigmentation disorder induced through contact with certain chemicals, most of which have a p-substituted phenol structure similar to the melanin precursor tyrosine. The tyrosinase-catalyzed oxidation of phenols to highly reactive o-quinone metabolites is a critical step in inducing leukoderma through the production of melanocyte-specific damage and immunological responses.

Objective: Our aim was to find an effective method to evaluate the formation of o-quinone by human tyrosinase and subsequent cellular reactions.