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https://www.readbyqxmd.com/read/28614705/a-uv-independent-topical-small-molecule-approach-for-melanin-production-in-human-skin
#1
Nisma Mujahid, Yanke Liang, Ryo Murakami, Hwan Geun Choi, Allison S Dobry, Jinhua Wang, Yusuke Suita, Qing Yu Weng, Jennifer Allouche, Lajos V Kemeny, Andrea L Hermann, Elisabeth M Roider, Nathanael S Gray, David E Fisher
The presence of dark melanin (eumelanin) within human epidermis represents one of the strongest predictors of low skin cancer risk. Topical rescue of eumelanin synthesis, previously achieved in "redhaired" Mc1r-deficient mice, demonstrated significant protection against UV damage. However, application of a topical strategy for human skin pigmentation has not been achieved, largely due to the greater barrier function of human epidermis. Salt-inducible kinase (SIK) has been demonstrated to regulate MITF, the master regulator of pigment gene expression, through its effects on CRTC and CREB activity...
June 13, 2017: Cell Reports
https://www.readbyqxmd.com/read/28607006/nr4a2-promotes-dna-double-strand-break-repair-upon-exposure-to-uvr
#2
Kelvin Yin, Yash Chhabra, Romain Tropée, Yi Chieh Lim, Mitchell Fane, Eloise Dray, Richard Sturm, Aaron G Smith
Exposure of melanocytes to ultraviolet radiation (UVR) induces the formation of UV-lesions that can produce deleterious effects in genomic DNA. Encounters of replication forks with unrepaired UV-lesions can lead to several complex phenomena, such as the formation of DNA double strand breaks (DSBs). The NR4A family of nuclear receptors are transcription factors that have been associated with mediating DNA repair functions downstream of the MC1R signalling pathway in melanocytes. In particular, emerging evidence shows that upon DNA damage, the NR4A2 receptor can translocate to sites of UV-lesion by mechanisms requiring post-translational modifications within the N-terminal domain and at a serine residue in the DNA biding domain at position 337...
June 12, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28599948/fish-pigmentation-and-the-melanocortin-system
#3
REVIEW
Laura Cal, Paula Suarez-Bregua, José Miguel Cerdá-Reverter, Ingo Braasch, Josep Rotllant
The melanocortin system is a complex neuroendocrine signaling mechanism involved in numerous physiological processes in vertebrates, including pigmentation, steroidogenesis and metabolic control. This review focuses at one of its most fascinating function in fish, its regulatory role in the control of pigmentation, in which the melanocortin 1 receptor (Mc1r), its agonist α-melanocyte stimulating hormone (α-Msh), and the endogenous antagonist agouti signaling protein (Asip1) are the main players. Functional control of Mc1r, which is highly expressed in fish skin and whose activation stimulates melanin production and melanosome dispersion in fish melanophores, is considered a key mechanism for vertebrate pigment phenotypes...
June 7, 2017: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
https://www.readbyqxmd.com/read/28599303/oleoylethanolamide-inhibits-%C3%AE-melanocyte-stimulating-hormone-stimulated-melanogenesis-via-erk-akt-and-creb-signaling-pathways-in-b16-melanoma-cells
#4
Juan Zhou, Tong Ren, Ying Li, Anran Cheng, Wanyi Xie, Lanxi Xu, Lu Peng, Jinbin Lin, Lianxiang Lian, Yong Diao, Xin Jin, Lichao Yang
The present study aimed to examine the potential inhibitory activity of oleoylethanolamide (OEA) on α-melanocyte stimulating hormone (α-MSH)-stimulated melanogenesis and the molecular mechanism(s) involved in the process in B16 mouse melanoma cells. Our data demonstrated that OEA markedly inhibited melanin synthesis and tyrosinase activity in α-MSH-stimulated B16 cells. In addition, the expression of melanogenesis-related proteins, such as melanocortin-1 receptor (MC1R), microphthalmia-associated transcription factor (MITF), tyrosinase-related protein-1 (TRP-1) and tyrosinase, was suppressed in a concentration-dependent manner by OEA...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28579117/key-amino-acid-residue-in-melanocortin-1-receptor-melanocyte-%C3%AE-msh-receptor-for-ligand-selectivity
#5
Yingkui Yang, Min Chen, George Ventro, Carroll M Harmon
The melanocortin-1 receptor (MC1R) is a subtype of the melanocortin receptor family and NDP-α-MSH is a non-selective agonist for MC1R. The core sequence of NDP-α-MSH, His-Phe-Arg-Trp, is important for ligand binding and biological activities at the melanocortin receptor subtypes (MCRs). A recent study indicates that Trp(9) in NDP-α-MSH plays an important role in ligand selectivity. Deletion of Trp(9) in NDP-α-MSH (des-Trp(9)-NDP-α-MSH) resulted in loss of agonist activity at MC4R, although remains agonist activity at MC1R...
June 1, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28502801/genome-wide-association-reveals-pigmentation-genes-play-a-role-in-skin-aging
#6
Matthew H Law, Sarah E Medland, Gu Zhu, Seyhan Yazar, Ana Viñuela, Leanne Wallace, Sri Niranjan Shekar, David L Duffy, Veronique Bataille, Dan Glass, Tim D Spector, Diane Wood, Scott D Gordon, Julie M Barbour, Anjali K Henders, Alex W Hewitt, Grant W Montgomery, Richard A Sturm, David A Mackey, Adèle C Green, Nicholas G Martin, Stuart MacGregor
Loss of fine skin patterning is a sign of both aging and photoaging. Studies investigating the genetic contribution to skin patterning offer an opportunity to better understand a trait that influences both physical appearance and risk of keratinocyte skin cancer. We undertook a meta-analysis of genome-wide association studies (GWAS) of a measure of skin pattern (microtopography score) damage in 1,671 twin pairs and 1,745 singletons (N = 5,087) drawn from three independent cohorts. We identified that rs185146 near SLC45A2 is associated with a skin aging trait (p = 4...
May 11, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28501589/genetic-modifiers-of-multiple-sclerosis-progression-severity-and-onset
#7
A Dessa Sadovnick, Anthony L Traboulsee, Yinshan Zhao, Cecily Q Bernales, Mary Encarnacion, Jay P Ross, Irene M Yee, Maria G Criscuoli, Carles Vilariño-Güell
The genetic contribution to clinical outcomes for multiple sclerosis (MS) has yet to be defined. We performed exome sequencing analysis in 100 MS patients presenting opposite extremes of clinical phenotype (discovery cohort), and genotyped variants of interest in 2016 MS patients (replication cohort). Linear and logistic regression analyses were used to identify significant associations with disease course, severity and onset. Our analysis of the discovery cohort nominated 38 variants in 21 genes. Replication analysis identified PSMG4 p...
July 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28491052/receptor-mediated-melanoma-targeting-with-radiolabeled-%C3%AE-melanocyte-stimulating-hormone-relevance-of-the-net-charge-of-the-ligand
#8
Jean-Philippe Bapst, Alex N Eberle
A majority of melanotic and amelanotic melanomas overexpress melanocortin type 1 receptors (MC1Rs) for α-melanocyte-stimulating hormone. Radiolabeled linear or cyclic analogs of α-MSH have a great potential as diagnostic or therapeutic tools for the management of malignant melanoma. Compounds such as [(111)In]DOTA-NAP-amide exhibit high affinity for the MC1R in vitro, good tumor uptake in vivo, but they may suffer from relatively high kidney uptake and retention in vivo. We have shown previously that the introduction of negative charges into radiolabeled DOTA-NAP-amide peptide analogs may enhance their excretion and reduce kidney retention...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28486572/evaluation-of-mc1r-high-throughput-nucleotide-sequencing-data-generated-by-the-1000-genomes-project
#9
Leonardo Arduino Marano, Letícia Marcorin, Erick da Cruz Castelli, Celso Teixeira Mendes-Junior
The advent of next-generation sequencing allows simultaneous processing of several genomic regions/individuals, increasing the availability and accuracy of whole-genome data. However, these new approaches may present some errors and bias due to alignment, genotype calling, and imputation methods. Despite these flaws, data obtained by next-generation sequencing can be valuable for population and evolutionary studies of specific genes, such as genes related to how pigmentation evolved among populations, one of the main topics in human evolutionary biology...
May 8, 2017: Genetics and Molecular Biology
https://www.readbyqxmd.com/read/28485764/%C3%A3-kad-kunskap-om-familj%C3%A3-rt-melanom-och-de-bakom%C3%A2-liggande-generna
#10
Hildur Helgadottir, Kari Nielsen, Veronica Höiom
Increased knowledge on familial melanoma and the underlying genetics Approximately 5-10 % of all melanoma patients have close relatives with melanoma. 5-20% of melanoma families have germline mutations in the CDKN2A gene. Swedish CDKN2A mutation carriers have a young median age of onset of melanoma, increased risks of multiple primary melanoma and of tobacco-associated cancers in respiratory and upper digestive tissues, and also worse survival compared to non-carriers. In up to 80% of melanoma families no high risk melanoma associated germline mutations are found...
May 9, 2017: Läkartidningen
https://www.readbyqxmd.com/read/28463841/skin-pigmentation-genetics-for-the-clinic
#11
Stephen A Ainger, Kasturee Jagirdar, Katie J Lee, H Peter Soyer, Richard A Sturm
Human pigmentation characteristics play an important role in the effects of sun exposure, skin cancer induction and disease outcomes. Several of the genes most important for this diversity are involved in the regulation and distribution of melanin pigmentation or enzymes involved in melanogenesis itself within the melanocyte cell present in the skin, hair and eyes. The single nucleotide polymorphisms and extended haplotypes within or surrounding these genes have been identified as risk factors for skin cancer, in particular, melanoma...
May 3, 2017: Dermatology: International Journal for Clinical and Investigative Dermatology
https://www.readbyqxmd.com/read/28452072/pgc-1%C3%AE-in-melanoma-a-key-factor-for-antioxidant-response-and-mitochondrial-function
#12
Margalida Torrens-Mas, Daniel González-Hedström, Marta Abrisqueta, Pilar Roca, Jordi Oliver, Jorge Sastre-Serra
Melanocortin 1 receptor (MC1R) and BRAF are common mutations in melanoma. Through different pathways, they each regulate the expression of PGC-1α, which is a key factor in the regulation of mitochondrial biogenesis and the antioxidant response. Our aim was to study the importance of the different regulatory characteristics of MC1R and BRAF on the pathways they regulate in melanoma. For this purpose, ROS production, levels of gene expression and enzymatic activities were analyzed in HBL and MeWo, with wild-type MC1R and BRAF, and A375 cells with mutant MC1R and BRAF...
April 27, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28442450/implementing-an-internet-delivered-skin-cancer-genetic-testing-intervention-to-improve-sun-protection-behavior-in-a-diverse-population-protocol-for-a-randomized-controlled-trial
#13
Jennifer L Hay, Marianne Berwick, Kate Zielaskowski, Kirsten Am White, Vivian M Rodríguez, Erika Robers, Dolores D Guest, Andrew Sussman, Yvonne Talamantes, Matthew R Schwartz, Jennie Greb, Jessica Bigney, Kimberly A Kaphingst, Keith Hunley, David B Buller
BACKGROUND: Limited translational genomic research currently exists to guide the availability, comprehension, and appropriate use of personalized genomics in diverse general population subgroups. Melanoma skin cancers are preventable, curable, common in the general population, and disproportionately increasing in Hispanics. OBJECTIVE: Variants in the melanocortin-1 receptor (MC1R) gene are present in approximately 50% of the population, are major factors in determining sun sensitivity, and confer a 2-to-3-fold increase in melanoma risk in the general population, even in populations with darker skin...
April 25, 2017: JMIR Research Protocols
https://www.readbyqxmd.com/read/28426141/melanocortin-2-3-and-4-receptor-gene-expressions-are-downregulated-in-cd8-t-cytotoxic-lymphocytes-and-cd19-b-lymphocytes-in-rheumatoid-arthritis-responding-to-tnf%C3%AE-inhibition
#14
Marlene Andersen, Ivan Nagaev, Michael Kruse Meyer, Olga Nagaeva, Jarl Wikberg, Lucia Mincheva-Nilsson, Grethe Neumann Andersen
Melanocortin signaling in leukocyte subsets elicits anti-inflammatory and immune tolerance inducing effects in animal experimental inflammation. In man, however, the effects of melanocortin signaling in inflammatory conditions have scarcely been examined. We explored the differential reactions of melanocortin 1-5 receptor (MC1-5R) gene expressions in pathogenetic leukocyte subsets in rheumatoid arthritis (RA) to treatment with TNFα inhibitor adalimumab. Seven patients with active RA donated blood at start and at three months treatment...
April 20, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28411032/a-2-bp-insertion-c-67_68inscc-in-mc1r-causes-recessive-white-coat-color-in-bama-miniature-pigs
#15
LETTER
Qitao Jia, Chunwei Cao, Hai Tang, Ying Zhang, Qiantao Zheng, Xiao Wang, Rui Zhang, Xianlong Wang, Ailing Luo, Hong Wei, Anming Meng, Qi Zhou, Hongmei Wang, Jianguo Zhao
No abstract text is available yet for this article.
April 20, 2017: Journal of Genetics and Genomics, Yi Chuan Xue Bao
https://www.readbyqxmd.com/read/28382689/p53-regulates-erk1-2-creb-cascade-via-a-novel-sash1-map2k2-crosstalk-to-induce-hyperpigmentation
#16
Ding'an Zhou, Zhongshu Kuang, Xing Zeng, Ke Wang, Jiangshu Ma, Huangchao Luo, Mei Chen, Yan Li, Jiawei Zeng, Shu Li, Fujun Luan, Yong He, Hongying Dai, Beizhong Liu, Hui Li, Lin He, Qinghe Xing
We previously reported that three point mutations in SASH1 and mutated SASH1 promote melanocyte migration in dyschromatosis universalis hereditaria (DUH) and a novel p53/POMC/Gαs/SASH1 autoregulatory positive feedback loop is regulated by SASH1 mutations to induce pathological hyperpigmentation phenotype. However, the underlying mechanism of molecular regulation to cause this hyperpigmentation disorder still remains unclear. In this study, we aimed to investigate the molecular mechanism undergirding hyperpigmentation in the dyschromatosis disorder...
April 6, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28382155/preclinical-melanoma-imaging-with-68-ga-labeled-%C3%AE-melanocyte-stimulating-hormone-derivatives-using-pet
#17
Chengcheng Zhang, Zhengxing Zhang, Kuo-Shyan Lin, Jinhe Pan, Iulia Dude, Navjit Hundal-Jabal, Nadine Colpo, François Bénard
It is estimated that melanoma accounted for 76,380 new cases and 10,130 deaths in the United States in 2016. The melanocortin 1 receptor (MC1R) is highly expressed in the vast majority of melanomas, which makes it an attractive target for molecular imaging and radionuclide therapy. Lactam bridge-cyclized α-melanocyte-stimulating hormone (Ac-Nle(4)-cyclo[Asp(5)-His-D-Phe(7)-Arg-Trp-Lys(10)]-NH2, or Nle-CycMSHhex) analogues have been successfully developed and studied for MC1R-targeted imaging, predominantly with single-photon emission computed tomography (SPECT)...
2017: Theranostics
https://www.readbyqxmd.com/read/28378841/%C3%AE-msh-and-melanocortin-receptors-at-early-ontogeny-in-european-sea-bass-dicentrarchus-labrax-l
#18
A Tsalafouta, M Gorissen, T N M Pelgrim, N Papandroulakis, G Flik, M Pavlidis
Temporal patterns of whole-body α-MSH concentrations and of transcripts of melanocortin receptors during early development as well as the endocrine response (α-MSH, cortisol, MCR mRNAs) to stress at the end of the larval period were characterized in Dicentrarchus labrax. Immunohistochemistry showed α-MSH positive cells in the pituitary pars intermedia in all stages examined. As development proceeds, α-MSH content gradually increases; mRNA levels of mc2r and mc4r remain low until first feeding where peak values are observed...
April 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28370617/genomic-evidence-for-convergent-evolution-of-a-key-trait-underlying-divergence-in-island-birds
#19
Elizabeth A Cooper, J Albert C Uy
Reproductive isolation can be initiated by changes in one or a few key traits that prevent random mating among individuals in a population. During the early stages of speciation, when isolation is often incomplete, there will be a heterogeneous pattern of differentiation across regions of the genome between diverging populations, with loci controlling these key traits appearing the most distinct as a result of strong diversifying selection. In this study, we used Illumina-sequenced ddRAD tags to identify genome-wide patterns of differentiation in three recently-diverged island populations of the Monarcha castaneiventris ycatcher of the Solomon Islands...
March 28, 2017: Molecular Ecology
https://www.readbyqxmd.com/read/28360400/cdkn2a-and-mc1r-variants-found-in-cypriot-patients-diagnosed-with-cutaneous-melanoma
#20
Georgia Koulermou, Christos Shammas, Andreas Vassiliou, Tassos C Kyriakides, Constantina Costi, Vassos Neocleous, Leonidas A Phylactou, Maria Pantelidou
The prevalence of genetic variants associated to cutaneous melanoma (CM) has never been determined within Cypriot melanomas. This study evaluates the frequency of variants in cyclin-dependent kinase inhibitor 2A (CDKN2A) and melanocortin-1 receptor (MC1R) in 32 patients diagnosed with CM. Other characteristics and risk factors were also assessed. CDKN2A p.Ala148Thr was detected in three of 32 patients, while the control group revealed no variations within CDKN2A. MC1R screening in 32 patients revealed the following variations: p...
March 2017: Journal of Genetics
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