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Kazumasa Wakamatsu

Kazumasa Wakamatsu
Institute for Melanin Chemistry、Fujita Health University

Emeritus Professor, Ph.D.

About

538
Publications
113,188
Reads
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20,581
Citations
Citations since 2017
117 Research Items
8176 Citations
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201720182019202020212022202305001,0001,500
201720182019202020212022202305001,0001,500
201720182019202020212022202305001,0001,500
Additional affiliations
April 2019 - present
Fujita Health University
Position
  • Professor Emeritus
September 1995 - July 1996
Newcastle University
Position
  • Research Associate
April 1988 - March 2019
Fujita Health University
Position
  • Professor (Full)

Publications

Publications (538)
Article
Color variation is a frequent evolutionary substrate for camouflage in small mammals, but the underlying genetics and evolutionary forces that drive color variation in natural populations of large mammals are mostly unexplained. The American black bear, Ursus americanus (U. americanus), exhibits a range of colors including the cinnamon morph, which...
Article
Full-text available
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...
Article
Full-text available
Malignant melanoma is one of the most malignant of all cancers. Melanoma occurs at the epidermo–dermal interface of the skin and mucosa, where small vessels and lymphatics are abundant. Consequently, from the onset of the disease, melanoma easily metastasizes to other organs throughout the body via lymphatic and blood circulation. At present, the m...
Article
Full-text available
TR1 and other selenoproteins have paradoxical effects in melanocytes and melanomas. Increasing selenoprotein activity with supplemental selenium in a mouse model of UV-induced melanoma prevents oxidative damage to melanocytes and delays melanoma tumor formation. However, TR1 itself is positively associated with progression in human melanomas and fa...
Preprint
Full-text available
Color variation is a frequent evolutionary substrate for camouflage in small mammals but the underlying genetics and evolutionary forces that drive color variation in natural populations of large mammals are mostly unexplained. The American black bear, Ursus americanus , exhibits a range of colors including the cinnamon morph which has a similar co...
Article
Full-text available
Human skin contains two distinct components: brown to black, insoluble eumelanin and light colored, alkaline‐soluble pheomelanin. Eumelanin consists of 5,6‐dihydroxyindole (DHI) and 5,6‐dihydroxyindole‐2‐carboxylic acid (DHICA) moieties, while pheomelanin consists of benzothiazine (BT) and benzothiazole (BZ) moieties. These melanin monomer units ca...
Article
Full-text available
Objective Patients with pro-opiomelanocortin (POMC) defects generally present with early-onset obesity, hyperphagia, hypopigmentation and adrenocorticotropin (ACTH) deficiency. Rodent models suggest that adequate cleavage of ACTH to α-melanocortin–stimulating hormone (α-MSH) and desacetyl-α-melanocortin–stimulating hormone (d-α-MSH) by prohormone c...
Article
Full-text available
A major advance in drug discovery and targeted therapy directed at cancer cells may be achieved by the exploitation and immunomodulation of their unique biological properties. This review summarizes our efforts to develop novel chemo-thermo-immunotherapy (CTI therapy) by conjugating a melanogenesis substrate, N-propionyl cysteaminylphenol (NPrCAP:...
Preprint
Full-text available
Colour is often used as an aposematic warning signal, with predator learning expected to lead to a single colour pattern within a population. However, there are many puzzling cases where aposematic signals are also polymorphic. The wood tiger moth, Arctia plantaginis , uses bright hindwing colours as a signal of unpalatability, and males have discr...
Article
Full-text available
Parkinson's disease (PD) is an aging-related disease and the second most common neuro-degenerative disease after Alzheimer's disease. The main symptoms of PD are movement disorders accompanied with deficiency of neurotransmitter dopamine (DA) in the striatum due to cell death of the nigrostriatal DA neurons. Two main histopathological hallmarks exi...
Article
Chemical leukoderma is an acquired depigmentation of the skin caused by repeated exposure to specific agents damaging to epidermal melanocytes. Case reports of chemical leukoderma have been associated with some consumer products. To date, there are no well-accepted approaches for evaluating and minimizing this risk. To this end, a framework is pres...
Article
Coloration traits are central to animal communication; they often govern mate choice, promote reproductive isolation and catalyse speciation. Specific genetic changes can cause variation in coloration, yet far less is known about how overall coloration patterns -which involve combinations of multiple colour patches across the body- can arise and ar...
Article
Pigment-producing melanocytes overcome frequent oxidative stress in their physiological role of protecting the skin against the deleterious effects of solar UV irradiation. This is accomplished by the activity of several endogenous antioxidant systems, including the thioredoxin antioxidant system, in which thioredoxin reductase 1 (TR1) plays an imp...
Article
Oculocutaneous albinism (OCA) 6 is a non‐syndromic type of OCA that has distinct ocular symptoms and variable cutaneous hypopigmentation. The causative gene of OCA6 is SLC24A5, which encodes NCKX5, a K+‐dependent Na+/Ca2+ exchanger 5. NCKX5 is involved in the maturation of melanosomes, but its function is still unclear. In this study, we characteri...
Article
Full-text available
Neurogenerative diseases, such as Parkinson’s disease, are associated, not only with the selective loss of dopamine (DA), but also with the accumulation of reactive catechol-aldehyde, 3,4-dihydroxyphenylacetaldehyde (DOPAL), which is formed as the immediate oxidation product of cytoplasmic DA by monoamine oxidase. DOPAL is well known to exhibit tox...
Article
To date no direct methods are available for the subunit quantification of pheomelanin, the sulfur-containing melanin form whose structure increases melanoma risk. Here we apply Raman spectroscopy combined with chemometrics (MCR-ALS method) to quantify benzothiazine (BT) and benzothiazole (BZ), the constituent monomers of pheomelanin. The Raman spec...
Article
In order to characterize the phenotype and to examine the effects of sun exposure on the color and structure of eumelanin (EM) and pheomelanin (PM) in alpaca fibers, we applied Soluene‐350 solubilization, alkaline hydrogen peroxide oxidation (AHPO) and hydroiodic acid (HI) hydrolysis to the base and tip fibers of 20 true‐black (TB) and 20 warm‐blac...
Article
Full-text available
Equol (7-hydroxy-3-(4′-hydroxyphenyl)-chroman, EQ), one of the major intestinally derived metabolites of daidzein, the principal isoflavane found in soybeans and most soy foods, has recently attracted increased interest as a health-beneficial compound for estrogen-dependent diseases. However, based on its structure with two p-substituted phenols, t...
Article
Ultraviolet (UV) light and incompletely understood genetic and epigenetic variations determine skin color. Here we describe an UV- and microphthalmia-associated transcription factor (MITF)-independent mechanism of skin pigmentation. Targeting the mitochondrial redox-regulating enzyme nicotinamide nucleotide transhydrogenase (NNT) resulted in cellul...
Chapter
It is known that melanin pigments composed of black to dark brown eumelanin (EM) and yellow to reddish-brown pheomelanin (PM) are widely distributed in vertebrates. Melanin pigments in vertebrate are produced in melanocytes which are distributed in the epidermis, hair follicles, choroid, iris, inner ear, and other tissues. The diversity of the colo...
Article
Full-text available
Solar ultraviolet B radiation (UVB) is one of the leading causes of various skin conditions, including photoaging, sunburn erythema and melanoma. As a protective response, the skin has inbuilt defense mechanisms, including DNA repair, cell cycle checkpoint, apoptosis, and melanin synthesis, of which DNA repair, cell cycle and apoptosis have been sh...
Article
Photoreactivity of melanin has become a major focus of research due to the postulated involvement of the pigment in UVA-induced melanoma. However, most of the hitherto studies were carried out using synthetic melanin models. Thus, photoreactivity of natural melanins is yet to be systematically analyzed. Here, we examined the photoreactive propertie...
Article
Melanins are widely distributed in animals and plants; in vertebrates, most melanins are present on the body surface. The diversity of pigmentation in vertebrates is mainly attributed to the quantity and ratio of eumelanin and pheomelanin synthesis. Most natural melanin pigments in animals consist of both eumelanin and pheomelanin in varying ratios...
Preprint
Full-text available
Mutations in the Cl-/H+ exchanger CLC7 and its subunit OSTM1 result in osteopetrosis, lysosomal disorders, and pigmentation defects in mice and humans. How CLC7/OSTM1 regulates pigmentation in skin and hair melanocytes remains unexplored. In human epidermal melanocytes, we found CLC7/OSTM1 localized to melanosomes, the organelles in which melanin i...
Article
Melanin synthesis occurs within a specialized organelle called the melanosome. Traditional methods for measuring melanin levels rely on the detection of chemical degradation products of melanin by high-performance liquid chromatography (HPLC). Although these methods are robust, they are unable to distinguish between melanin synthesis and degradatio...
Article
A mid-infrared free-electron laser (MIR-FEL) is a synchrotron-radiation-based femto-to pico-second pulse laser. It has unique characteristics such as variable wavelengths in the infrared region and an intense pulse energy. So far, MIR-FELs have been utilized to perform multi-photon absorption reactions against various gas molecules and protein aggr...
Article
Residual melanins have been detected in multimillion-year-old animal body fossils; however, confident identification and characterization of these natural pigments remain challenging due to loss of chemical signatures during diagenesis. Here, we simulate this post-burial process through artificial maturation experiments using three synthetic and on...
Article
Melanin is an important phenolic skin pigment found throughout the animal kingdom. Tyrosine and its hydroxylated product dopa provide the starting material for melanin biosynthesis in all animals. Through a set of well-established reactions, they are converted to 5,6-dihydroxyindole (DHI) and DHI-2-carboxylic acid (DHICA). Oxidative polymerization...
Article
The exposure of human skin to 4-(4-hydroxyphenyl)-2-butanone (raspberry ketone, RK) is known to cause chemical/occupational leukoderma. RK is a carbonyl derivative of 4-(4-hydroxyphenyl)-2-butanol (rhododendrol), a skin whitening agent that was found to cause leukoderma in skin of many consumers. These two phenolic compounds are oxidized by tyrosin...
Article
Tyrosinase catalyzes the oxidation of phenols and catechols (o-diphenols) to o-quinones. The reactivities of o-quinones thus generated are responsible for oxidative browning of plant products, sclerotization of insect cuticle, defense reaction in arthropods, tunichrome biochemistry in tunicates, production of mussel glue, and most importantly melan...
Article
Alkaline hydrogen peroxide oxidation (AHPO) of eumelanin and pheomelanin, two major classes of melanin pigments, affords pyrrole-2,3,5-tricarboxylic acid (PTCA), pyrrole-2,3-dicarboxylic acid (PDCA) and pyrrole-2,3,4,5-tetracarboxylic acid (PTeCA) from eumelanin and thiazole-2,4,5-tricarboxylic acid (TTCA) and thiazole-4,5-dicarboxylic acid (TDCA)...
Article
Post‐inflammatory hyperpigmentation (PIH) is a common cutaneous condition that can cause a disfigured appearance. However, the pathophysiology of PIH remains poorly understood, at least in part, because an appropriate animal model for research has not been established. In order to analyze the pathomechanism of PIH, we successfully induced PIH in a...
Article
Full-text available
It is believed that while eumelanin plays photoprotective and antioxidant role in pigmented tissues, pheomelanin being more photoreactive could behave as a phototoxic agent. Although the metal ion-sequestering ability of melanin might be protective, transition metal ions present in natural melanins could affect their physicochemical properties. The...
Article
When aging, melanin in human retinal pigment epithelium (RPE) undergoes oxidative modifications, which increase its photoreactivity and reduce antioxidant capacity, elevating the risk of chronic phototoxicity to the retina. The aim of this research was to examine the effect of iron on degradation of melanin induced by hydrogen peroxide and light, a...
Article
Full-text available
Melanoma is one of the most lethal and malignant cancers and its incidence is increasing worldwide, and Japan is not an exception. Although there are numerous therapeutic options for melanoma, the prognosis is still poor once it has metastasized. The main concern after removal of a primary melanoma is whether it has metastasized, and early detectio...
Article
Full-text available
Melanosomes (melanin-bearing organelles) are common in the fossil record occurring as dense packs of globular microbodies. the organic component comprising the melanosome, melanin, is often preserved in fossils, allowing identification of the chemical nature of the constituent pigment. In present-day vertebrates, melanosome morphology correlates wi...
Article
Melanin-based colorations in birds constitute a paradigm for the study of the molecular basis of phenotypic variation. variation in the melanocortin-1 receptor (MCR1) gene, a key regulator of melanin synthesis in feather melanocytes, can lead to changes in the production of melanin and hence in feather colour. Here we investigate the proximate mech...
Article
Screening pigments are essential for vision in animals. Vertebrates use melanins bound in melanosomes as screening pigments, whereas cephalopods are assumed to use ommochromes. Preserved eye melanosomes in the controversial fossil Tullimonstrum (Mazon Creek, IL, USA) are partitioned by size and/or shape into distinct layers. These layers resemble t...
Poster
Melanoma is a highly aggressive cancer that exhibits metastasis to various critical organs. One of the most characteristic features of melanoma is its ability to synthesize melanin pigment. However, for mostly unknown reasons, pigmentation of melanoma cells seems to be disrupted in standard 2D culture. This significantly limits research in the fiel...
Article
Full-text available
Fossilized eyes permit inferences of the visual capacity of extinct arthropods1–3. However, structural and/or chemical modifications as a result of taphonomic and diagenetic processes can alter the original features, thereby necessitating comparisons with modern species. Here we report the detailed molecular composition and microanatomy of the eyes...
Article
Full-text available
Fossils are a key source of data on the evolution of feather structure and function through deep time, but their ability to resolve macroevolutionary questions is compromised by an incomplete understanding of their taphonomy. Critically, the relative preservation potential of two key feather components, melanosomes and keratinous tissue, is not ful...
Article
Full-text available
Significance Recent reports of nonintegumentary melanosomes in fossils hint at functions for melanin beyond color production, but the biology and evolution of internal melanins are poorly understood. Our results show that internal melanosomes are widespread in diverse fossil and modern vertebrates and have tissue-specific geometries and metal chemi...
Article
Homozygous loss of function of the melanocortin 1 receptor (MC1R) is associated with a pheomelanotic pigment phenotype and increased melanoma risk. MC1R heterozygosity is less well studied, although individuals inheriting one loss‐of‐function MC1R allele are also melanoma‐prone. Using the K14‐Scf C57BL/6J animal model whose skin is characterized by...
Article
Full-text available
In a previous study, we showed that the size of melanosomes isolated from Japanese female hairs enlarges with age, and this affects the hair color. In this study, we analyzed the age-dependent changes in hair melanin in order to further explore the factors related to hair color changing by aging. A significant positive correlation with age was foun...
Article
trans‐Resveratrol (3,5,4'‐trihydroxy‐trans‐stilbene, RES), a naturally occurring polyphenol, has recently attracted increased interest as a health‐beneficial agent. However, based on its p‐substituted phenol structure, RES is expected to be a substrate for tyrosinase and to produce a toxic o‐quinone metabolite. The results of this study demonstrate...
Article
Full-text available
In dynamic selection regimes, an honest signal that indicates high quality in favorable environments might be negatively related to quality in unfavorable environments, though empirical evidence is scarce. Here, we studied the relationship between plumage ornaments and physiological state in the Pacific swallow Hirundo tahitica on Amami Oshima Isla...
Article
Full-text available
Neuromelanin (NM) is a dark brown pigment found in dopaminergic neurons of the substantia nigra (SN) and in norepinephrinergic neurons of the locus coeruleus (LC). Although NM is thought to be involved in the etiology of Parkinson’s disease (PD) because its content decreases in neurodegenerative diseases such as PD, details are still unknown. In th...
Article
Full-text available
Recent progress has been made in paleontology with respect to resolving pigmentation in fossil material. Morphological identification of fossilized melanosomes has been one approach, while a second methodology using chemical imaging and spectroscopy has also provided critical information particularly concerning eumelanin (black pigment) residue. In...
Article
The domesticated rock pigeon (Columba livia) has been bred for hundreds of years to display an immense variety of ornamental attributes such as feather color and color patterns. Color is influenced by multiple loci that impact the type and amount of melanin deposited on the feathers. Pigeons homozygous for the “recessive red” mutation, which causes...
Article
Adaptive evolution in new or changing environments can be difficult to predict because the functional connections between genotype, phenotype, and fitness are complex. Here, we make these explicit connections by combining field and laboratory experiments in wild mice. We first directly estimate natural selection on pigmentation traits and an underl...
Article
Alcohol induces various cutaneous changes, such as palmar erythema and jaundice. However, alcohol-induced skin hyperpigmentation due to melanin deposition has not been reported. Aldehyde dehydrogenase 2 (ALDH2), one of 19 human ALDH isozymes, metabolizes endogenous and exogenous aldehydes to their respective carboxylic acids. Reduced ALDH2 greatly...
Article
Full-text available
Pigment‐based plumage coloration and its physiological properties have attracted many researchers to explain the evolution of such ornamental traits. These studies, however, assume the functional importance of the predominant pigment while ignoring that of other minor pigments, and few studies have focused on the composition of these pigments. Usin...
Article
Full-text available
Background: Oculocutaneous albinism (OCA) results in reduced melanin synthesis, skin hypopigmentation, increased risk of UV-induced malignancy, and developmental eye abnormalities affecting vision. No treatments exist. We have shown that oral nitisinone increases ocular and fur pigmentation in a mouse model of one form of albinism, OCA-1B, due to...
Article
BACKGROUND. Oculocutaneous albinism (OCA) results in reduced melanin synthesis, skin hypopigmentation, increased risk of UV-induced malignancy, and developmental eye abnormalities affecting vision. No treatments exist. We have shown that oral nitisinone increases ocular and fur pigmentation in a mouse model of one form of albinism, OCA-1B, due to h...
Article
Serum 5-S-cysteinyldopa (5-S-CD) has been reported as a diagnostic marker of malignant melanoma, but its utility as a biomarker for targeted therapy remains unknown. We assessed serum 5-S-CD in 8 patients with metastatic melanoma (median age : 64.5 years) who were treated with targeted agents at Shinshu University Hospital between 2014 and 2016. 5-...
Article
Full-text available
Ichthyosaurs are extinct marine reptiles that display a notable external similarity to modern toothed whales. Here we show that this resemblance is more than skin deep. We apply a multidisciplinary experimental approach to characterize the cellular and molecular composition of integumental tissues in an exceptionally preserved specimen of the Early...
Article
Pheomelanin-based plumage pigmentation has been suggested to be an honest signal of individual quality to conspecifics. It has been hypothesized that oxidative stress is an important agent linking pheomelanic pigmentation to individual quality. Using the Asian barn swallow Hirundo rustica gutturalis, a wild passerine, we tested whether the pheomela...
Article
The forces driving evolution remain controversial. In fungi, are they Darwinian, Neo-Lamarckian or both? To help provide an answer, we performed an experimental study involving transplantation of soil at 'Evolution Canyon', Israel, from a south-facing, tropical, savanna, high solar radiation, 'African' slope (AS) to a north-facing temperate foreste...