Melanocortin 1 Receptor (MC1R): Pharmacological and Therapeutic Aspects

Mun, Yeung Chul; Kim, Woo Hyun; Shin, Dongyun

doi:10.3390/ijms241512152

Cited by 10 publications

(4 citation statements)

References 126 publications

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“…For example, Slominski et al [66], using in vitro and in vivo models, demonstrated that stimulation of melanogenesis leads to increased expression of HIF-1α and its subsequent translocation into the nucleus. Thus, it is possible that HIF-1α is induced by the production of intermediates of melanogenesis, including massive generation of reactive oxygen species [4,67,68]. Consequently, the initiation of melanogenesis affects the expression of multiple genes involved in regulating the behavior of melanocytes and melanoma cells, including the metabolic switch to glycolysis coordinated by HIF-1.…”

Section: Discussionmentioning

confidence: 99%

Melanogenesis Is Directly Affected by Metabolites of Melatonin in Human Melanoma Cells

Möller,

Linowiecka,

Gagat

et al. 2023

IJMS

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Melatonin (N-acetyl-5-methoxytryptamine, MEL), its kynurenic (N1-acetyl-N2-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 N-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.

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Section: Discussionmentioning

confidence: 99%

Melanogenesis Is Directly Affected by Metabolites of Melatonin in Human Melanoma Cells

Möller,

Linowiecka,

Gagat

et al. 2023

IJMS

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“…MC1R is a member of the melanocortin receptors (MCRs) subfamily, belonging to the G-protein-coupled receptors (GPCR). It has a high affinity for the α-MSH and its binding results in the production of darker eumelanin (García-Borrón et al, 2014;Mun et al, 2023). In contrast, ASIP competitively antagonizes α-MSH, and when it binds to MC1R, it stimulates the synthesis of the red or yellow phaeomelanin (Abdel-Malek et al, 1999).…”

Section: G Ene Ti C Ba S Is and Adap Tive E Voluti On Of S K In Colou...mentioning

confidence: 99%

Skin colour: A window into human phenotypic evolution and environmental adaptation

Liu,

Bitsue,

Yang

2024

Molecular Ecology

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As modern humans ventured out of Africa and dispersed around the world, they faced novel environmental challenges that led to geographic adaptations including skin colour. Over the long history of human evolution, skin colour has changed dramatically, showing tremendous diversity across different geographical regions, for example, the majority of individuals from the expansive lands of Africa have darker skin, whereas the majority of people from Eurasia exhibit lighter skin. What adaptations did lighter skin confer upon modern humans as they migrated from Africa to Eurasia? What genetic mechanisms underlie the diversity of skin colour observed in different populations? In recent years, scientists have gradually gained a deeper understanding of the interactions between pigmentation gene and skin colour through population‐based genomic studies of different groups around the world, particularly in East Asia and Africa. In this review, we summarize our current understanding of 26 skin colour‐related pigmentation genes and 48 SNPs that influence skin colour. Important pigmentation genes across three major populations are described in detail: MFSD12, SLC24A5, PDPK1 and DDB1/CYB561A3/TMEM138 influence skin colour in African populations; OCA2, KITLG, SLC24A2, GNPAT and PAH are key to the evolution of skin pigmentation in East Asian populations; and SLC24A5, SLC45A2, TYR, TYRP1, ASIP, MC1R and IRF4 significantly contribute to the lightening of skin colour in European populations. We summarized recent findings in genomic studies of skin colour in populations that implicate diverse geographic environments, local adaptation among populations, gene flow and multi‐gene interactions as factors influencing skin colour diversity.

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“…Eumelanin produced by melanocytes is influenced by five known distinct melanocortin receptors. Dersimelagon has the highest affinity for the melanocortin-1 receptor (MC1R), a G-protein coupled receptor on melanocytes that binds to melanocortin to regulate skin and hair color (Table 3) [40][41][42]. MC1R is established as the main driver of human pigmentation [34].…”

Section: Mechanism Of Actionmentioning

confidence: 99%

Illuminating Dersimelagon: A Novel Agent in the Treatment of Erythropoietic Protoporphyria and X-Linked Protoporphyria

Madigan,

Rudnick,

Agnew

et al. 2023

Pharmaceuticals

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Erythropoietic protoporphyria (EPP) is a genetic disorder stemming from reduced ferrochelatase expression, the final enzyme in the pathway of heme biosynthesis. A closely related condition, X-linked protoporphyria (XLP), bears similar clinical features although it arises from the heightened activity of δ-aminolevulinic acid synthase 2 (ALAS2), the first and normally rate-controlling enzyme in heme biosynthesis in developing red blood cells. Both of these abnormalities result in the buildup of protoporphyrin IX, leading to excruciating light sensitivity and, in a minority of cases, potentially fatal liver complications. Traditionally, managing EPP and XLP involved sun avoidance. However, the emergence of innovative therapies, such as dersimelagon, is reshaping the therapeutic landscape for these conditions. In this review, we summarize salient features of the properties of dersimelagon, shedding light on its potential role in advancing our understanding of treatment options for EPP and XLP.

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Melanocortin 1 Receptor (MC1R): Pharmacological and Therapeutic Aspects

Cited by 10 publications

References 126 publications

Melanogenesis Is Directly Affected by Metabolites of Melatonin in Human Melanoma Cells

Melanogenesis Is Directly Affected by Metabolites of Melatonin in Human Melanoma Cells

Skin colour: A window into human phenotypic evolution and environmental adaptation

Illuminating Dersimelagon: A Novel Agent in the Treatment of Erythropoietic Protoporphyria and X-Linked Protoporphyria

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