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melanocortin receptor

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https://www.readbyqxmd.com/read/28229938/participation-of-ghrelin-signalling-in-the-reciprocal-regulation-of-hypothalamic-npy-pomc-mediated-appetite-control-in-amphetamine-treated-rats
#1
Ching-Han Yu, Shu-Chen Chu, Pei-Ni Chen, Yih-Shou Hsieh, Dong-Yih Kuo
Hypothalamic neuropeptide Y (NPY) and proopiomelanocortin (POMC) have been documented to participate in amphetamine (AMPH)-induced appetite suppression. This study investigated whether ghrelin signalling is associated with changes in NPY/POMC-mediated appetite control. Rats were given AMPH daily for four days, and changes in food intake, body weight, plasma ghrelin, hypothalamic NPY, melanocortin 3 receptor (MC3R), ghrelin O-acyltransferase (GOAT), acyl ghrelin (AG) and ghrelin receptor (GHSR1a) were examined and compared...
February 13, 2017: Appetite
https://www.readbyqxmd.com/read/28228747/from-bioinactive-acth-to-acth-antagonist-the-clinical-perspective
#2
REVIEW
Chiraz Ghaddhab, Jean-Marc Vuissoz, Johnny Deladoëy
The adrenocorticotropic hormone (ACTH) is a pituitary hormone derived from a larger peptide, the proopiomelanocortin (POMC), as are the MSHs (α-MSH, β-MSH, and γ-MSH) and the β-LPH-related polypeptides (Figure 1A). ACTH drives adrenal steroidogenesis and growth of the adrenal gland. ACTH is a 39 amino acid polypeptide that binds and activates its cognate receptor [melanocortin receptor 2 (MC2R)] through the two regions H6F7R8W9 and K15K16R17R18P19. Most POMC-derived polypeptides contain the H6F7R8W9 sequence that is conserved through evolution...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28220105/acth-receptor-mc2r-specificity-what-do-we-know-about-underlying-molecular-mechanisms
#3
REVIEW
Davids Fridmanis, Ance Roga, Janis Klovins
Coincidentally, the release of this Research Topic in Frontiers in Endocrinology takes place 25 years after the discovery of the adrenocorticotropic hormone receptor (ACTHR) by Mountjoy and colleagues. In subsequent years, following the discovery of other types of mammalian melanocortin receptors (MCRs), ACTHR also became known as melanocortin type 2 receptor (MC2R). At present, five types of MCRs have been reported, all of which share significant sequence similarity at the amino acid level, and all of which specifically bind melanocortins (MCs)-a group of biologically active peptides generated by proteolysis of the proopiomelanocortin precursor...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28218067/melanocortin-4-receptor-gene-mutations-in-a-group-of-turkish-obese-children-and-adolescents
#4
Selma Tunç, Korcan Demir, Fatma Ajlan Tükün, Cihan Topal, Filiz Hazan, Burcu Sağlam, Özlem Nalbantoğlu, Melek Yıldız, Behzat Özkan
OBJECTIVE: Melanocortin-4 receptor (MC4R) mutations are the most common known cause of monogenic obesity but there is limited data regarding MC4R mutations in Turkish subjects. To determine the prevalence of MC4R mutations in a group of Turkish morbid obese children and adolescents. METHODS: MC4R was sequenced in 47 consecutive morbidly obese children and adolescents (28 girls and 19 boys, aged 1-18 years) who presented during a 1-year period. Inclusion criterion was a BMI ≥120% of the 95th percentile or ≥35 kg/m2...
February 20, 2017: Journal of Clinical Research in Pediatric Endocrinology
https://www.readbyqxmd.com/read/28214221/relationship-between-the-melanocortin-1-receptor-mc1r-variant-r306ter-and-physiological-responses-to-mechanical-or-thermal-stimuli-in-labrador-retriever-dogs
#5
Tania E Perez, Katrina L Mealey, Neal S Burke, Tamara L Grubb, Michael H Court, Stephen A Greene
OBJECTIVE: Variants in the MC1R gene have been associated with red hair color and sensitivity to pain in humans. The study objective was to determine if a relationship exists between MC1R genotype and physiological thermal or mechanical nociceptive thresholds in Labrador Retriever dogs. STUDY DESIGN: Prospective experimental study. ANIMALS: Thirty-four Labrador Retriever dogs were included in the study following public requests for volunteers...
January 11, 2017: Veterinary Anaesthesia and Analgesia
https://www.readbyqxmd.com/read/28213370/promiscuity-among-the-mraps
#6
Adrian J L Clark, Li F Chan
The melanocortin 2 receptor accessory protein (MRAP) was originally discovered to be an essential co-receptor for the ACTH receptor/melanocortin 2 receptor, and it physically interacts with this receptor and is required for receptor trafficking and ligand binding. A related molecule, MRAP2, is mainly expressed in the CNS and appears to have a role with the melanocortin 4 receptor. Consistent with this is the observation that a massively obese phenotype develops when the Mrap2 gene is deleted in mice. However, the characteristics of this phenotype differ from those of Mc4r deleted mice, and suggest that an additional role, possibly resulting from an interaction with other receptors is possible...
February 17, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28207798/altered-hepatic-lipid-metabolism-in-mice-lacking-both-the-melanocortin-type-4-receptor-and-low-density-lipoprotein-receptor
#7
Vera Lede, Andrej Meusel, Antje Garten, Yulia Popkova, Melanie Penke, Christin Franke, Albert Ricken, Angela Schulz, Wieland Kiess, Daniel Huster, Torsten Schöneberg, Jürgen Schiller
Obesity is often associated with dyslipidemia and hepatosteatosis. A number of animal models of non-alcoholic fatty liver disease (NAFLD) are established but they significantly differ in the molecular and biochemical changes depending on the genetic modification and diet used. Mice deficient for melanocortin type 4 receptor (Mc4rmut) develop hyperphagia, obesity, and subsequently NAFLD already under regular chow and resemble more closely the energy supply-driven obesity found in humans. This animal model was used to assess the molecular and biochemical consequences of hyperphagia-induced obesity on hepatic lipid metabolism...
2017: PloS One
https://www.readbyqxmd.com/read/28197776/effects-of-melanocortin-4-receptor-agonists-and-antagonists-on-expression-of-genes-related-to-reproduction-in-spotted-scat-scatophagus-argus
#8
Dong-Neng Jiang, Jian-Tao Li, Ya-Xiong Tao, Hua-Pu Chen, Si-Ping Deng, Chun-Hua Zhu, Guang-Li Li
Melanocortin-4 receptor (Mc4r) function related to reproduction in fish has not been extensively investigated. Here, we report on gene expression changes by real-time PCR following treatment with Mc4r agonists and antagonists in the spotted scat (Scatophagus argus). Using in vitro incubated hypothalamus, the Mc4r nonselective agonist NDP-MSH ([Nle(4), D-Phe(7)]-α-melanocyte stimulating hormone; 10(-6) M) and selective agonist THIQ (N-[(3R)-1, 2, 3, 4-Tetrahydroisoquinolinium-3-ylcarbonyl]- (1R)-1-(4-chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazol-1-ylmethyl) piperidin-1-yl]-2-oxoethylamine; 10(-7) M) significantly increased the expression of gnrh (Gonadotropin releasing hormone), while the Mc4r nonselective antagonist SHU9119 (Ac-Nle-[Asp-His-DPhe/DNal(2')-Arg-Trp-Lys]-NH2; 10(-6) M) and selective antagonist Ipsen 5i (compound 5i synthesized in Ipsen Research Laboratories; 10(-6) M) significantly inhibited gnrh expression after 3 h of incubation...
February 14, 2017: Journal of Comparative Physiology. B, Biochemical, Systemic, and Environmental Physiology
https://www.readbyqxmd.com/read/28152402/molecular-cloning-tissue-distribution-and-pharmacological-characterization-of-melanocortin-4-receptor-in-grass-carp-ctenopharyngodon-idella
#9
L Li, Z Yang, Y-P Zhang, S He, X-F Liang, Y-X Tao
Melanocortin-4 receptor (MC4R) plays a pivotal role in the mediation of leptin action on food intake and energy expenditure in mammals. The MC4R has also been identified in several teleosts, and its importance in the regulation of fish energy homeostasis is emerging. We herein reported on the molecular cloning, tissue distribution, and pharmacological characterization of MC4R in grass carp (Ctenopharyngodon idella), an economically and ecologically important fish. We showed that grass carp MC4R (ciMC4R) consisted of a 981 bp open reading frame encoding a protein of 326 amino acids, highly homologous (>95%) to several teleost MC4Rs...
November 21, 2016: Domestic Animal Endocrinology
https://www.readbyqxmd.com/read/28150230/melanocortin-receptor-4-gene-polymorphisms-in-glioblastoma-patients-treated-with-concomitant-radio-chemotherapy
#10
Francesco Pasqualetti, Paola Orlandi, Vittorio Simeon, Martina Cantarella, Daniela Giuliani, Teresa Di Desidero, Alessandra Gonnelli, Durim Delishaj, Giuseppe Lombardi, Andrea Sechi, Marc Sanson, Vittorina Zagonel, Fabiola Paiar, Romano Danesi, Salvatore Guarini, Guido Bocci
Melanocortins are peptides with well-recognized antiinflammatory and neuroprotective activity. No data are currently available on melanocortin receptor-4 (MC4R) gene polymorphisms and tumors, including glioblastomas (GBMs), or their relationship with radiotherapy or chemotherapy. The aim of this study was to evaluate the possible predictive/prognostic role of the MC4R SNPs on GBM patients. Fifty-five patients with a proven diagnosis of GBM, treated with radiotherapy and temozolomide, were consecutively enrolled...
February 1, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28148682/dietary-protein-modifies-the-effect-of-the-mc4r-genotype-on-2-year-changes-in-appetite-and-food-craving-the-pounds-lost-trial
#11
Tao Huang, Yan Zheng, Adela Hruby, Donald A Williamson, George A Bray, Yiru Shen, Frank M Sacks, Lu Qi
BACKGROUND: The melanocortin-4 receptor (MC4R) plays a pivotal role in the regulation of appetite and eating behavior. Variants in the MC4R gene have been related to appetite and obesity. OBJECTIVE: We aimed to examine whether weight-loss diets modified the effect of the "obesity-predisposing" MC4R genotype on appetite-related measures in a randomized controlled trial. METHODS: A total of 811 overweight and obese subjects [25 ≤ body mass index (BMI; kg/m(2)) ≤ 40] aged 30-70 y were included in the 2-y POUNDS Lost (Preventing Overweight Using Novel Dietary Strategies) trial...
February 1, 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28146118/jun-dimerization-protein-2-activates-mc2r-transcriptional-activity-role-of-phosphorylation-and-sumoylation
#12
Chiung-Min Wang, Raymond X Wang, Runhua Liu, Wei-Hsiung Yang
Jun dimerization protein 2 (JDP2), a basic leucine zipper transcription factor, is involved in numerous biological and cellular processes such as cancer development and regulation, cell-cycle regulation, skeletal muscle and osteoclast differentiation, progesterone receptor signaling, and antibacterial immunity. Though JDP2 is widely expressed in mammalian tissues, its function in gonads and adrenals (such as regulation of steroidogenesis and adrenal development) is largely unknown. Herein, we find that JDP2 mRNA and proteins are expressed in mouse adrenal gland tissues...
January 31, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28138237/preparation-cytotoxicity-and-in-vivo-antitumor-efficacy-of-111-in-labeled-modular-nanotransporters
#13
Tatiana A Slastnikova, Andrey A Rosenkranz, Natalia B Morozova, Maria S Vorontsova, Vasiliy M Petriev, Tatiana N Lupanova, Alexey V Ulasov, Michael R Zalutsky, Raisa I Yakubovskaya, Alexander S Sobolev
PURPOSE: Modular nanotransporters (MNTs) are a polyfunctional platform designed to achieve receptor-specific delivery of short-range therapeutics into the cell nucleus by receptor-mediated endocytosis, endosome escape, and targeted nuclear transport. This study evaluated the potential utility of the MNT platform in tandem with Auger electron emitting (111)In for cancer therapy. METHODS: Three MNTs developed to target either melanocortin receptor-1 (MC1R), folate receptor (FR), or epidermal growth factor receptor (EGFR) that are overexpressed on cancer cells were modified with p-SCN-Bn-NOTA and then labeled with (111)In in high specific activity...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28132916/characterization-of-ligand-binding-to-melanocortin-4-receptors-using-fluorescent-peptides-with-improved-kinetic-properties
#14
Reet Link, Santa Veiksina, Ago Rinken, Sergei Kopanchuk
Melanocortin 4 (MC4) receptors are important drug targets as they regulate energy homeostasis, eating behaviour and sexual functions. The ligand binding process to these G protein-coupled receptors is subject to considerable complexity. Different steps in the complex dynamic regulation can be characterized by ligand binding kinetics. Optimization of these kinetic parameters in terms of on-rate and residence time can increase the rapid onset of drug action and reduce off-target effects. Fluorescence anisotropy (FA) is one of the homogeneous fluorescence-based assays that enable continuous online monitoring of ligand binding kinetics...
January 26, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28132887/pc1-3-deficiency-impacts-pro-opiomelanocortin-processing-in-human-embryonic-stem-cell-derived-hypothalamic-neurons
#15
Liheng Wang, Lina Sui, Sunil K Panigrahi, Kana Meece, Yurong Xin, Jinrang Kim, Jesper Gromada, Claudia A Doege, Sharon L Wardlaw, Dieter Egli, Rudolph L Leibel
We recently developed a technique for generating hypothalamic neurons from human pluripotent stem cells. Here, as proof of principle, we examine the use of these cells in modeling of a monogenic form of severe obesity: PCSK1 deficiency. The cognate enzyme, PC1/3, processes many prohormones in neuroendocrine and other tissues. We generated PCSK1 (PC1/3)-deficient human embryonic stem cell (hESC) lines using both short hairpin RNA and CRISPR-Cas9, and investigated pro-opiomelanocortin (POMC) processing using hESC-differentiated hypothalamic neurons...
February 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28128928/a-direct-in-vivo-comparison-of-the-melanocortin-monovalent-agonist-ac-his-dphe-arg-trp-nh2-versus-the-bivalent-agonist-ac-his-dphe-arg-trp-pedg20-his-dphe-arg-trp-nh2-a-bivalent-advantage
#16
Cody J Lensing, Danielle N Adank, Stacey L Wilber, Katie T Freeman, Sathya M Schnell, Robert Charles Speth, Adam T Zarth, Carrie Haskell-Luevano
Bivalent ligands targeting putative melanocortin receptor dimers have been developed and characterized in vitro, however studies of their functional in vivo effects have been limited. The current report compares the effects of homobivalent ligand CJL-1-87, Ac-His-DPhe-Arg-Trp-PEDG20-His-DPhe-Arg-Trp-NH2, to monovalent ligand CJL-1-14, Ac-His-DPhe-Arg-Trp-NH2 on energy homeostasis in mice after central intracerebroventricular (ICV) administration into the lateral ventricle of the brain. Bivalent ligand CJL-1-87 had noteworthy advantages as an anti-obesity probe over CJL-1-14 in a fasting-refeeding in vivo paradigm...
January 27, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28103316/alpha-melanocyte-stimulating-hormone-protects-against-cytokine-induced-barrier-damage-in-caco-2-intestinal-epithelial-monolayers
#17
Judit Váradi, András Harazin, Ferenc Fenyvesi, Katalin Réti-Nagy, Péter Gogolák, György Vámosi, Ildikó Bácskay, Pálma Fehér, Zoltán Ujhelyi, Gábor Vasvári, Eszter Róka, David Haines, Mária A Deli, Miklós Vecsernyés
Alpha-melanocyte-stimulating hormone (α-MSH) is a potent anti-inflammatory peptide with cytoprotective effect in various tissues. The present investigation demonstrates the ability of α-MSH to interact with intestinal epithelial cell monolayers and mitigate inflammatory processes of the epithelial barrier. The protective effect of α-MSH was studied on Caco-2 human intestinal epithelial monolayers, which were disrupted by exposure to tumor necrosis factor-α and interleukin-1β. The barrier integrity was assessed by measuring transepithelial electric resistance (TEER) and permeability for marker molecules...
2017: PloS One
https://www.readbyqxmd.com/read/28094871/divergence-of-camp-signaling-pathways-mediating-augmented-nucleotide-excision-repair-and-pigment-induction-in-melanocytes
#18
Erin M Wolf Horrell, Stuart G Jarrett, Katharine M Carter, John A D'Orazio
Loss-of-function melanocortin 1 receptor (MC1R) polymorphisms are common in UV-sensitive fair-skinned individuals and are associated with blunted cAMP second messenger signaling and higher lifetime risk of melanoma because of diminished ability of melanocytes to cope with UV damage. cAMP signaling positions melanocytes to resist UV injury by up-regulating synthesis of UV-blocking eumelanin pigment and by enhancing the repair of UV-induced DNA damage. cAMP enhances melanocyte nucleotide excision repair (NER), the genome maintenance pathway responsible for the removal of mutagenic UV photolesions, through cAMP-activated protein kinase (protein kinase A)-mediated phosphorylation of the ataxia telangiectasia mutated and Rad3 related (ATR) protein on the S435 residue...
January 17, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28093215/melanocortin-4-receptor-constitutive-activity-inhibits-l-type-voltage-gated-calcium-channels-in-neurons
#19
F Agosti, S Cordisco Gonzalez, V Martinez Damonte, M J Tolosa, N Di Siervi, H B Schioth, C Davio, M Perello, J Raingo
The melanocortin 4 receptor (MC4R) is a G protein-coupled receptor (GPCR) that is expressed in several brain nuclei playing a crucial role in the regulation of energy balance controlling the homeostasis of the organism. It displays both agonist-evoked and constitutive activity, and moreover, it can couple to different G proteins. Most of the research on MC4R has been focused on agonist-induced activity, while the molecular and cellular basis of MC4R constitutive activity remains scarcely studied. We have previously shown that neuronal N-type voltage-gated calcium channels (CaV2...
January 16, 2017: Neuroscience
https://www.readbyqxmd.com/read/28081251/physical-activity-and-sedentary-behaviors-modify-the-association-between-melanocortin-4-receptor-gene-variant-and-obesity-in-chinese-children-and-adolescents
#20
Jie-Yun Song, Qi-Ying Song, Shuo Wang, Jun Ma, Hai-Jun Wang
Effects of MC4R variants in previous Chinese population studies were inconsistent. Gene-environment interactions might influence the effect of MC4R variants on obesity, which was still unclear. We performed the study to clarify the association of variants near MC4R gene with obesity-related phenotypes and gene-environment interactions in Chinese children and adolescents. Two common variants (rs12970134 and rs17782313) near MC4R were genotyped in 2179 children and adolescents aged 7-18 years in Beijing of China...
2017: PloS One
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