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https://www.readbyqxmd.com/read/29770870/development-of-a-novel-ligand-binding-assay-for-relaxin-family-peptide-receptor-3-and-4-using-nanoluc-complementation
#1
Meng-Jun Hu, Xiao-Xia Shao, Hao-Zheng Li, Wei-Han Nie, Jia-Hui Wang, Ya-Li Liu, Zeng-Guang Xu, Zhan-Yun Guo
Relaxin family peptides perform a variety of biological functions by binding and activating relaxin family peptide receptor 1-4 (RXFP1-4), four A-class G protein-coupled receptors. In the present work, we developed a novel ligand binding assay for RXFP3 and RXFP4 based on NanoLuc complementation technology (NanoBiT). A synthetic ligation version of the low-affinity small complementation tag (SmBiT) was efficiently ligated to the A-chain N terminus of recombinant chimeric agonist R3/I5 using recombinant circular sortase A...
May 16, 2018: Amino Acids
https://www.readbyqxmd.com/read/29722152/modulation-of-forebrain-function-by-nucleus-incertus-and-relaxin-3-rxfp3-signaling
#2
REVIEW
Francisco E Olucha-Bordonau, Héctor Albert-Gascó, Francisco Ros-Bernal, Valeria Rytova, Emma K E Ong-Pålsson, Sherie Ma, Ana M Sánchez-Pérez, Andrew L Gundlach
The nucleus incertus (NI) in the pontine tegmentum sends ascending projections to the midbrain, hypothalamus, amygdala, basal forebrain, hippocampus, and prefrontal cortex, and has a postulated role in modulating several forebrain functions. A substantial population of GABAergic NI neurons expresses the neuropeptide, relaxin-3, which acts via the Gi/o -protein-coupled receptor, RXFP3, present throughout the forebrain target regions. Broad and specific manipulations of these systems by activation or inhibition of the NI or modulating RXFP3 signaling have revealed key insights into the likely influence of the NI/relaxin-3/RXFP3 system on modalities including arousal, feeding, stress responses, anxiety and addiction, and attention and memory...
May 2, 2018: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29716533/genome-wide-copy-number-variant-analysis-reveals-variants-associated-with-10-diverse-production-traits-in-holstein-cattle
#3
Yang Zhou, Erin E Connor, George R Wiggans, Yongfang Lu, Robert J Tempelman, Steven G Schroeder, Hong Chen, George E Liu
BACKGROUND: Copy number variation (CNV) is an important type of genetic variation contributing to phenotypic differences among mammals and may serve as an alternative molecular marker to single nucleotide polymorphism (SNP) for genome-wide association study (GWAS). Recently, GWAS analysis using CNV has been applied in livestock, although few studies have focused on Holstein cattle. RESULTS: We describe 191 CNV detected using intensity data from over 700,000 SNP genotypes generated with the BovineHD Genotyping BeadChip (Illumina, San Diego, CA) in 528 Holstein cows...
May 2, 2018: BMC Genomics
https://www.readbyqxmd.com/read/29716428/the-subset-of-patients-with-acute-heart-failure-able-to-secrete-relaxin-2-at-pregnancy-concentrations-could-have-a-longer-survival-a-pilot-study
#4
Òscar Miró, Pablo Herrero-Puente, Belén Prieto, María García-García, Pablo García-Hernández, Francisco J Martín-Sánchez, Javier Jacob, José Ríos, Rodolfo Romero, Víctor Gil, Étienne Gayat, Pere Llorens, Alexandre Mebazaa
OBJECTIVE: To investigate how many patients with acute heart failure (AHF) hypersecrete relaxin-2 concentrations similar to those of pregnant women and determine their long-term outcome. METHODS: In consecutive AHF patients relaxin-2 was quantified by ELISA sandwich method. Patients were divided into pregnancy-like group (PLG, relaxin-2 ≥ 500 pg/mL) and control group (CG, relaxin-2 < 500 pg/mL). The primary outcome was all-cause death during follow-up...
May 1, 2018: Biomarkers: Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals
https://www.readbyqxmd.com/read/29715504/the-biology-and-evolution-of-the-dilp8-lgr3-pathway-a-relaxin-like-pathway-coupling-tissue-growth-and-developmental-timing-control
#5
REVIEW
Alisson M Gontijo, Andres Garelli
Many insects, like cockroaches, moths, and flies, can regenerate tissues by extending the growth-competent phases of their life cycle. The molecular and cellular players mediating this coordination between tissue growth and developmental timing have been recently discovered in Drosophila. The insulin/relaxin-like peptide, Dilp8, was identified as a factor communicating abnormal growth status of Drosophila larval imaginal discs to the neuroendocrine centers that control the timing of the onset of metamorphosis...
April 28, 2018: Mechanisms of Development
https://www.readbyqxmd.com/read/29710689/pulmonary-hemodynamic-effects-and-pulmonary-arterial-compliance-during-hypovolemic-shock-and-reinfusion-with-human-relaxin-2-serelaxin-treatment-in-a-sheep-model
#6
René Schiffner, Thomas Lehmann, Sabine J Bischoff, Timo Zippelius, Marius Nistor, Martin Schmidt
BACKGROUND: Previous studies on the recombinant form of human relaxin-2 (serelaxin) have shown a decrease of pulmonary hemodynamics after serelaxin injection. Currently, the effect of serelaxin treatment during hypovolemia in a large animal model remains mostly unknown. METHODS: 12 sheep were randomly assigned to a sham or serelaxin (30μg/kg serelaxin) group and underwent right heart catheterization. 50% of the estimated total blood volume were removed to induce hypovolemia, and subsequently retransfused 20 min later (reinfusion)...
April 14, 2018: Clinical Hemorheology and Microcirculation
https://www.readbyqxmd.com/read/29695398/chromatin-immunoprecipitation-and-dna-sequencing-identified-a-lims1-ilk-pathway-regulated-by-lmo1-in-neuroblastoma
#7
Norihisa Saeki, Akira Saito, Yuki Sugaya, Mitsuhiro Amemiya, Hiroe Ono, Rie Komatsuzaki, Kazuyoshi Yanagihara, Hiroki Sasaki
BACKGROUND/AIM: Overall survival for the high-risk group of neuroblastoma (NB) remains at 40-50%. An integrative genomics study revealed that LIM domain only 1 (LMO1) encoding a transcriptional regulator to be an NB-susceptibility gene with a tumor-promoting activity, that needs to be revealed. MATERIALS AND METHODS: We conducted chromatin immunoprecipitation and DNA sequencing analyses and cell proliferation assays on two NB cell lines. RESULTS: We identified three genes regulated by LMO1 in the cells, LIM and senescent cell antigen-like domains 1 (LIMS1), Ras suppressor protein 1 (RSU1) and relaxin 2 (RLN2)...
May 2018: Cancer Genomics & Proteomics
https://www.readbyqxmd.com/read/29623915/the-relaxin-peptide-family-potential-future-hope-for-neuroprotective-therapy-a-short-review
#8
REVIEW
Marius Nistor, Martin Schmidt, René Schiffner
Since its discovery in the 1920's the relaxin peptide hormone family has not only grown in number to now seven members (relaxin-1, relaxin-2, relaxin-3, insulin-like peptide (INSL) 3, INSL4, INSL5 and INSL6), but ever more effects, suchs as vasodilatory, angiogenic, anti-apoptopic, anti-fibriotic and anti-inflammatory, have been linked to them. While relaxin-2 has mainly been investigated in the context of cardiac protection, most comprehensively in the RELAX-AHF and RELAX AHF2 studies, a small number of studies have furthermore assessed the potential neuroprotective effects of especially relaxin-2 and other members of the relaxin family...
March 2018: Neural Regeneration Research
https://www.readbyqxmd.com/read/29623045/relaxin-deficiency-leads-to-uterine-artery-dysfunction-during-pregnancy-in-mice
#9
Sarah A Marshall, Sevvandi N Senadheera, Maria Jelinic, Kelly O'Sullivan, Laura J Parry, Marianne Tare
The uterine vasculature undergoes profound adaptations in response to pregnancy. Augmentation of endothelial vasodilator function and reduced smooth muscle reactivity are factors contributing to uterine artery adaptation and are critical for adequate placental perfusion. The peptide hormone relaxin has an important role in mediating the normal maternal renal vascular adaptations during pregnancy through a reduction in myogenic tone and an increase in flow-mediated vasodilation. Little is known however about the influence of endogenous relaxin on the uterine artery during pregnancy...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29601823/cholesterol-modulates-the-binding-properties-of-human-relaxin-family-peptide-receptor-3-with-its-ligands
#10
Jia-Hui Wang, Meng-Jun Hu, Xiao-Xia Shao, Dian Wei, Ya-Li Liu, Zeng-Guang Xu, Zhan-Yun Guo
Relaxin family peptide receptor 3 (RXFP3) is implicated in the regulation of food intake and stress response upon activation by its cognate agonist relaxin-3. As an A-class G protein-coupled receptor, RXFP3 is an integral plasma membrane protein with seven transmembrane domains, yet influence of the membrane lipids on its function remains unknown. In the present study, we disclosed that cholesterol, an essential membrane lipid for mammalian cells, modulated the binding properties of human RXFP3 with its ligands...
March 27, 2018: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29575065/evidence-for-the-role-of-insl3-on-sperm-production-in-boars-by-passive-immunisation
#11
I Minagawa, Y Murata, K Terada, M Shibata, E Y Park, H Sasada, T Kohsaka
Insulin-like factor 3 (INSL3), previously called relaxin-like factor, is essential for foetal testis descent and has been implicated in sperm production in adult males. This study investigated the role of INSL3 in sperm production by examining the effect of neutralising INSL3 by passive immunisation on testicular function and sperm output in boars. Six male Duroc boars were randomly assigned to passive immunisation and control groups (n = 3 each). The immunisation group was intravenously injected with an IgG fraction of anti-INSL3 antibody developed against the B domain of INSL3 at 2-week intervals from 21-40 weeks of age...
March 25, 2018: Andrologia
https://www.readbyqxmd.com/read/29565035/associations-between-serum-relaxin-2-aneurysm-formation-size-and-severity-of-atherosclerosis-a-preliminary-prospective-analysis
#12
Konstantinos Papoutsis, Alkistis Kapelouzou, Diamantis I Tsilimigras, Nikolaos Patelis, Georgios Kouvelos, Dimitrios Schizas, Ioannis Karavokyros, Sotirios Georgopoulos
Serum relaxin 2 (RL2) is a pleiotropic hormone that acts on various organs and systems, particularly the cardiovascular system. Although RL2 seems to upregulate the synthesis of nitric monoxide (NO) and matrix metalloproteinase (MMP)-2 and -9, current literature on its role in atherosclerosis and aneurysm formation is scarce. The aim of this study was to investigate the levels of serum RL2 in patients with an arterial aneurysm as well as in atherosclerotic patients, and correlate them with the severity of their related vascular disease...
March 22, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29536410/relaxin-2-fails-to-lower-intraocular-pressure-and-to-dilate-retinal-vessels-in-rats
#13
Ulrike Hampel, Katharina Träger, Hanhan Liu, Julia Teister, Franz Grus, Verena Prokosch-Willing
PURPOSE: Recently, the vasodilator relaxin 2 has been introduced as a treatment for acute heart failure. However, its role on vessels of the eye and intraocular pressure (IOP) remains unclear though it has been hypothesized to induce a decrease IOP after intramuscular injection in humans. We aimed to test whether the hormone relaxin 2 lowers IOP and dilates retinal vessels in animals. METHODS: The IOP of female Sprague-Dawley rats before and after application of relaxin 2 was measured using an Icare Tonolab device calibrated for rats...
March 13, 2018: International Ophthalmology
https://www.readbyqxmd.com/read/29533760/abnormal-extracellular-matrix-remodelling-in-the-cervix-of-pregnant-relaxin-deficient-mice-is-not-associated-with-reduced-matrix-metalloproteinase-expression-or-activity
#14
Sarah A Marshall, Jonathan T McGuane, Yu May Soh, Helen M Gehring, Emma Simpson, Laura J Parry
Relaxin regulates cervical extracellular matrix (ECM) remodelling during pregnancy by modifying collagen and other ECM molecules by unknown mechanisms. We hypothesised that abnormal collagen remodelling in the cervix of pregnant relaxin-deficient (Rln1-/-) mice is due to excessive collagen (Col1a1 and Col3a1) and decreased matrix metalloproteinases (Mmp2, Mmp9, Mmp13 and Mmp7) and oestrogen receptors (Esr1 and Esr2). Quantitative polymerase chain reaction, gelatinase zymography, MMP activity assays and histological staining evaluated changes in ECM in pregnant wildtype (Rln1+/+) and Rln1-/- mice...
March 14, 2018: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/29526354/heart-disease-and-relaxin-new-actions-for-an-old-hormone
#15
REVIEW
Teja Devarakonda, Fadi N Salloum
The hormone relaxin has long been recognized for its involvement in maternal adaptation during pregnancy. However, discoveries during the past two decades on the mechanism of action of relaxin, its family of receptors, and newly described roles in attenuating ischemia/reperfusion (I/R) injury, inflammation, and arrhythmias have prompted vast interest in exploring its therapeutic potential in cardiovascular disease. These observations inspired recently concluded clinical trials in patients with acute heart failure...
May 2018: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/29513121/serum-relaxin-2-as-a-novel-biomarker-for-prostate-cancer
#16
Y Xu, Q Yu, Y Liu
No abstract text is available yet for this article.
March 7, 2018: British Journal of Biomedical Science
https://www.readbyqxmd.com/read/29491682/relaxin-influences-ileal-muscular-activity-through-a-dual-signaling-pathway-in-mice
#17
Eglantina Idrizaj, Rachele Garella, Fabio Francini, Roberta Squecco, Maria Caterina Baccari
AIM: To investigate the signaling pathways involved in the relaxin (RLX) effects on ileal preparations from mice through mechanical and electrophysiological experiments. METHODS: For mechanical experiments, ileal preparations from female mice were mounted in organ baths containing Krebs-Henseleit solution. The mechanical activity was recorded via force-displacement transducers, which were coupled to a polygraph for continuous recording of isometric tension. Electrophysiological measurements were performed in current- and voltage-clamp conditions by a microelectrode inserted in a single smooth muscle cell (SMC) of the ileal longitudinal layer...
February 28, 2018: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29479354/withaferin-a-associated-differential-regulation-of-inflammatory-cytokines
#18
Seema Dubey, Hyunho Yoon, Mark Steven Cohen, Prakash Nagarkatti, Mitzi Nagarkatti, Dev Karan
A role of inflammation-associated cytokines/chemokines has been implicated in a wide variety of human diseases. Here, we investigated the regulation of inflammatory cytokines released by monocyte-derived THP-1 cells following treatment with the dietary agent withaferin A (WFA). Membrane-based cytokine array profiling of the culture supernatant from adenosine triphosphate-stimulated WFA-treated THP-1 cells showed differential regulation of multiple cytokines/chemokines. A selected group of cytokines/chemokines [interleukin-1 beta (IL-1β), CCL2/MCP-1, granulocyte-macrophage colony stimulating factor, PDGF-AA, PTX3, cystatin-3, relaxin-2, TNFRSF8/CD30, and ACRP30] was validated at the transcription level using qPCR...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29466617/synthesis-and-characterization-of-the-r27s-genetic-variant-of-insulin-like-peptide-5
#19
Alexander N Zaykov, Vasily M Gelfanov, Fa Liu, Richard D DiMarchi
We report the synthesis and in vitro bioactivity assessment for an insulin-like peptide 5 (INSL5) analogue that was recently discovered as a genetic mutation in an Amish population. The mutation was associated with improved metabolic status, and receptor-based antagonism was proposed as a potential mechanism for the altered phenotype. We determined the specific peptide analogue to be fully potent and of maximal efficacy at the human relaxin family peptide receptor 4 (RXFP4), suggesting an alternative basis for the observed effect...
April 23, 2018: ChemMedChem
https://www.readbyqxmd.com/read/29458108/the-relaxin-receptor-as-a-therapeutic-target-perspectives-from-evolution-and-drug-targeting
#20
REVIEW
Ross A D Bathgate, Martina Kocan, Daniel J Scott, M Akhter Hossain, Sara V Good, Sergey Yegorov, Jan Bogerd, Paul R Gooley
The peptide relaxin was first identified as an important circulating hormone during pregnancy over 90 years ago. Research over many years defined the numerous biological roles that relaxin plays throughout pregnancy in many mammalian species. These important biological actions have led to the testing of relaxin as a therapeutic agent for a number of indications. The discovery of the relaxin receptor, RXFP1, in 2002 facilitated the better understanding of the cellular targets of relaxin, its mechanism of action and enabled the development of relaxin mimetics and screening for small molecule agonists...
February 17, 2018: Pharmacology & Therapeutics
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