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In this study, the antimelanogenic effect of an ethyl acetate fraction of Oroxylum indicum Vent. seeds (OISEA) and its underlying mechanisms in melan-a cells were investigated. Antimelanogenesis activity was confirmed by assessing inhibition of tyrosinase activity and melanin content in the cells. Both transcriptional and translational expression of microphthalmia-associated transcription factor (MITF), tyrosinase, and tyrosinase related protein-1 and 2 (TYRP-1 and TYRP-2), were also examined. The results depicted that pretreatment of OISEA significantly inhibits not only tyrosinase activity, but melanin production and intracellular tyrosinase activity. By repressing the expression of tyrosinase, TYRP-1, TYRP-2, and MITF, OISEA interrupted melanin production. Additionally, OISEA interfered with the phosphorylation of p38, extracellular signal-regulated kinase 1/2 (ERK1/2), and c-Jun N-terminal kinase (JNK), with the reversal of OISEA-induced melanogenesis inhibition after treatment with the specific inhibitors SB239063, U0126, and SP600125. Overall, these results suggest that OISEA can stimulate p38, ERK1/2, JNK phosphorylation, and subsequent suppression of melanin, leading to the inhibition of melanogenic enzymes and melanin production, possibly owing to the presence of polyphenolic compounds. [ABSTRACT FROM AUTHOR]

Melanin is the main pigment responsible for the color of human skin, hair and eye. Its biosynthesis requires three melanogenic enzymes, tyrosinase (TYR), and the tyrosinase-related proteins TYRP1 and TYRP2. The difficulty of isolating pure and homogeneous proteins from endogenous sources has hampered their study, and resulted in many contradictory findings regarding their physiological functions. In this review, we summarize recent advances on the structure and function of TYR and TYRPs by virtue of the crystal structure of human TYRP1, which is the first available structure of a mammalian melanogenic enzyme. This structure, combined with tyrosinase structures from other lower eukaryotes and mutagenesis studies of key active site residues, sheds light on the mechanism of TYR and TYRPs. Furthermore, a TYRP1-based homology model of TYR provides a high-quality platform to map and analyze albinism-related mutations, as well as the design of specific antimelanogenic compounds. Finally, we provide perspectives for future structure/function studies of TYR and TYRPs. [ABSTRACT FROM AUTHOR]

Human malignant melanoma is a common primary malignant cutaneous tumour derived from transformed epidermal melanocytes. Patients with melanoma have a high rate of mortality due to resistance to chemotherapeutic drugs, a major obstacle to a successful treatment. Several reports have suggested that CD146 plays an important role as a signalling molecule in human melanoma. This role includes CD146 as a participant in inflammation, differentiation, adhesion, tumourigenicity, metastasis, invasion and angiogenesis among other processes, which suggests that this molecule promotes the progression of human melanoma as a multifaceted regulator. In this article, we explore the effects and corresponding mechanisms with respect to the role of CD146/ MUC18 in the promotion of human melanoma progression. Collectively, the studies indicated that targeting CD146, because it is a suitable marker of poor patient outcome, might be useful in the design of future strategies for the prevention and treatment of human melanoma. [ABSTRACT FROM AUTHOR]

Melanogenesis is the process of generating pigmentation via melanin synthesis and delivery. Three key enzymes, tyrosinase, tyrosinase-related protein 1 (TRP1) and TRP2, metabolize melanin from L-tyrosine. Melanin synthesizing enzymes are regulated by microphthalmia-associated transcription factor (MITF). The titrated extract of Centella asiatica (TECA) contains the major components asiatic acid, asiaticoside and madecassic acid. The present study revealed that TECA reduces the melanin content in melanocytes. Moreover, the asiaticoside contained in TECA modulated melanogenesis by inhibiting tyrosinase mRNA expression. The decrease in tyrosinase mRNA levels was mediated through MITF. Uniquely, asiaticoside inhibited MITF by decreasing its DNA binding affinity. In conclusion, the results of the present study indicate that asiaticoside treatment may have beneficial effects in hyperpigmentation diseases or for skin whitening. [ABSTRACT FROM AUTHOR]

The presence of melanocytes in the oral epithelium is a well-established fact, but their physiological functions are not well defined. Melanin provides protection from environmental stressors such as ultraviolet radiation and reactive oxygen species; and melanocytes function as stress-sensors having the capacity both to react to and to produce a variety of microenvironmental cytokines and growth factors, modulating immune, inflammatory and antibacterial responses. Melanocytes also act as neuroendocrine cells producing local neurotransmitters including acetylcholine, catecholamines and opioids, and hormones of the melanocortin system such as proopiomelanocortin, adrenocorticotropic hormone and α-melanocyte stimulating hormone, that participate in intracellular and in intercellular signalling pathways, thus contributing to tissue homeostasis. There is a wide range of normal variation in melanin pigmentation of the oral mucosa. In general, darker skinned persons more frequently have oral melanin pigmentation than lights-kinned persons. Variations in oral physiological pigmentation are genetically determined unless associated with some underlying disease. In this article, we discuss some aspects of the biophysiology of oral melanocytes, of the functions of melanin, and of physiological oral pigmentation. [ABSTRACT FROM AUTHOR]

The melanocytes in vitiligo repigmentation are derived predominantly from melanocyte precursors (MPs) present in the outer root sheath (ORS) of hair follicles. The methods currently used for culturing MPs are unstable, and the cultured cells have the capacity to produce melanin. These factors are problematic when conducting in vitro studies to investigate the mechanism of repigmentation. Although 1,25-dihydroxyvitamin D3 (VID) has been demonstrated to be highly effective in the treatment of vitiligo in the clinic, its precise mode of action has yet to be elucidated. In the present study, the method for the culture of MPs from the ORS of hair follicles was optimized and the ability of VID to activate MPs was investigated. The results suggested that the MPs cultured using the optimized method mainly exhibited bipolar morphology. The cells proliferated well and were negative for 3,4-dihydroxy-L-phenylalanine (DOPA) staining. Transmission electron microscopy revealed that the cytoplasm of the MPs contained numerous stage I and stage II melanosomes; however, stage III and IV melanosomes were not observed. Following VID treatment, the MPs showed increased dendritic morphology, the cells stained positive for DOPA and stage III and IV melanosomes appeared in the cells. Western blotting revealed that microphthalmia-associated transcription factor (MITF), tyrosinase (TYR), tyrosinase-related protein-1 (TRP-1) and TRP-2 were expressed in the MPs and that VID increased the expression levels of MITF, TYR and TRP-1. However, the levels of MITF, TYR and TRP-1 in the MPs prior to and following VID treatment were significantly lower compared with those in cultured epidermal melanocytes, while the levels of TRP-2 in these three groups were not significantly different. Subsequent to VID treatment, the TYR activity in the MPs increased significantly, as did the corresponding melanin levels. In conclusion, the present study successfully optimized the method for MP culture. The MPs demonstrated no significant TYR activity or melanin synthesis; therefore, the MP cultures exhibited the features of MPs in vivo. In addition, VID significantly promoted the differentiation of MPs. [ABSTRACT FROM AUTHOR]

Melanosome biogenesis requires successive waves of cargo delivery from endosomes to immature melanosomes, coupled with recycling of the trafficking machinery. Dennis et al. (2016. J. Cell Biol. http ://dx .doi .org /10 .1083 /jcb .201605090) report differential roles for BLOC-1 and BLOC-3 complexes in delivery and recycling of melanosomal biogenetic components, supplying directionality to melanosome maturation. [ABSTRACT FROM AUTHOR]

The treatment of Riehl's melanosis is difficult and challenging. Recently, a low-fluence 1064-nm quality (Q)-switched neodymium: yttrium-aluminum-garnet (Nd: YAG) laser method, referred to as 'laser toning', has been used in the treatment of melasma in Asian countries. We present here a series of cases of Riehl's melanosis that were treated effectively with a novel Q-switched Nd: YAG laser that was operated as a dual-pulse at half-fluence and 140-μs intervals. [ABSTRACT FROM AUTHOR]