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Relaxin

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https://www.readbyqxmd.com/read/28161795/a-novel-bret-based-binding-assay-for-interaction-studies-of-relaxin-family-peptide-receptor-3-with-its-ligands
#1
Jia-Hui Wang, Xiao-Xia Shao, Meng-Jun Hu, Dian Wei, Ya-Li Liu, Zeng-Guang Xu, Zhan-Yun Guo
Relaxin family peptide receptor 3 (RXFP3) is an A-class G protein-coupled receptor that is implicated in the regulation of food intake and stress response upon activation by its cognate agonist relaxin-3. To study its interaction with various ligands, we developed a novel bioluminescence resonance energy transfer (BRET)-based binding assay using the brightest NanoLuc as an energy donor and a newly developed cyan-excitable orange fluorescent protein (CyOFP) as an energy acceptor. An engineered CyOFP without intrinsic cysteine residues but with an introduced cysteine at the C-terminus was overexpressed in Escherichia coli and chemically conjugated to the A-chain N-terminus of an easily labeled chimeric R3/I5 peptide via an intermolecular disulfide linkage...
February 4, 2017: Amino Acids
https://www.readbyqxmd.com/read/28122716/relaxin-confers-cytotrophoblast-protection-from-hypoxiareoxygenation-injury-through-the-phosphatidylinositol-3-kinase-akt-protein-kinase-b-cell-survival-pathway
#2
Oluseyi Ogunleye, Bertha Campo, Diana Herrera, Emiel D Post Uiterweer, Kirk P Conrad
Preeclampsia affects 3-5% of pregnancies, contributes to 10-15% of maternal mortality, and is a leading cause of prematurity and increased long-term morbidity in those affected. Contemporary understanding of preeclampsia's maternal-fetal interface suggests a major role for placental oxidative stress resulting from ischemia-reperfusion injury. We hypothesized the pregnancy hormone relaxin would reduce cytotrophoblast apoptosis, necrosis (aponecrosis) and export of placental debris into maternal circulation. If so, relaxin might be employed as a therapeutic intervention to diminish activation of the maternal systemic inflammatory response central to clinical disease development...
January 25, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28120574/relaxin-modulates-the-expression-of-mmps-and-timps-in-fibroblasts-of-patients-with-carpal-tunnel-syndrome
#3
Young Mi Kang, Hwan Mo Lee, Seong Hwan Moon, Ho Kang, Yun Rak Choi
PURPOSE: The aim of this study was to investigate the anti-fibrotic effect of relaxin in subsynovial fibroblasts activated by transforming growth factor beta (TGF-β). MATERIALS AND METHODS: To test the anti-fibrotic effect of an adenovirus-relaxin construct (Ad-RLN) on subsynovial fibroblasts in vitro, cells from subsynovial connective tissue of patients with carpal tunnel syndrome were activated with TGF-β1 and exposed to Ad-RLN (as a therapeutic gene) or adenovirus-lacZ construct (as a marker gene) for four hours...
March 2017: Yonsei Medical Journal
https://www.readbyqxmd.com/read/28108636/serelaxin-treatment-promotes-adaptive-hypertrophy-but-does-not-prevent-heart-failure-in-experimental-peripartum-cardiomyopathy
#4
Justus Nonhoff, Melanie Ricke-Hoch, Mirco Mueller, Britta Stapel, Tobias Pfeffer, Martina Kasten, Michaela Scherr, Constantin von Kaisenberg, Johann Bauersachs, Arash Haghikia, Denise Hilfiker-Kleiner
AIMS: Peripartum cardiomyopathy (PPCM) is a systolic left ventricular dysfunction developing in the peripartum phase in previously healthy women. Relaxin-2 is a pregnancy hormone with potential beneficial effects in heart failure patients. We evaluated Relaxin-2 as a potential diagnostic marker and/or a therapeutic agent in PPCM. METHODS AND RESULTS: In healthy peripartum women, serum Relaxin-2 levels (measured by ELISA in the second half of pregnancy) were elevated showing a decreasing trend in the first postpartum week and returned to non-pregnant levels thereafter...
January 20, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28100033/relaxin-3-inputs-target-hippocampal-interneurons-and-deletion-of-hilar-relaxin-3-receptors-in-floxed-rxfp3-mice-impairs-spatial-memory
#5
M Haidar, G Guèvremont, C Zhang, Rad Bathgate, E Timofeeva, C M Smith, A L Gundlach
Hippocampus is innervated by γ-aminobutyric acid (GABA) 'projection' neurons of the nucleus incertus (NI), including a population expressing the neuropeptide, relaxin-3 (RLN3). In studies aimed at gaining an understanding of the role of RLN3 signaling in hippocampus via its Gi/o -protein-coupled receptor, RXFP3, we examined the distribution of RLN3-immunoreactive nerve fibres and RXFP3 mRNA-positive neurons in relation to hippocampal GABA neuron populations. RLN3-positive elements were detected in close-apposition with a substantial population of somatostatin (SST)- and GABA-immunoreactive neurons, and a smaller population of parvalbumin- and calretinin-immunoreactive neurons in different hippocampal areas, consistent with the relative distribution patterns of RXFP3 mRNA and these marker transcripts...
January 18, 2017: Hippocampus
https://www.readbyqxmd.com/read/28098344/inhibition-of-oxytocin-and-vasopressin-neuron-activity-in-rat-hypothalamic-paraventricular-nucleus-by-relaxin-3-rxfp3-signalling
#6
Alan Kania, Anna Czerw, Agnieszka Grabowiecka, Camila de Ávila, Tomasz Blasiak, Zenon Rajfur, Marian H Lewandowski, Grzegorz Hess, Elena Timofeeva, Andrew L Gundlach, Anna Blasiak
KEY-POINTS: Relaxin-3 is a stress-responsive neuropeptide that acts at its cognate receptor, RXFP3, to alter behaviours including feeding. In this study, we have demonstrated a direct, RXFP3-dependent, inhibitory action of relaxin-3 on oxytocin and vasopressin PVN neuron electrical activity, a putative cellular mechanism of orexinergic actions of relaxin-3. We observed a Gαi/o -protein-dependent inhibitory influence of selective RXFP3 activation on PVN neuronal activity in vitro and demonstrated a direct action of RXFP3 activation on oxytocin and vasopressin PVN neurons, confirmed by their abundant expression of RXFP3 mRNA...
January 18, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28088197/production-of-human-pro-relaxin-h2-in-the-yeast-pichia-pastoris
#7
D Cimini, K Della Corte, R Finamore, L Andreozzi, A Stellavato, A V A Pirozzi, F Ferrara, R Formisano, M De Rosa, M Chino, L Lista, A Lombardi, V Pavone, C Schiraldi
BACKGROUND: Initially known as the reproductive hormone, relaxin was shown to possess other therapeutically useful properties that include extracellular matrix remodeling, anti-inflammatory, anti-ischemic and angiogenic effects. All these findings make relaxin a potential drug for diverse medical applications. Its precursor, pro-relaxin, is an 18 kDa protein, that shows activity in in vitro assays. Since extraction of relaxin from animal tissues raises several issues, prokaryotes and eukaryotes were both used as expression systems for recombinant relaxin production...
January 14, 2017: BMC Biotechnology
https://www.readbyqxmd.com/read/28081371/gwas-identifies-new-loci-for-painful-temporomandibular-disorder
#8
A E Sanders, D Jain, T Sofer, K F Kerr, C C Laurie, J R Shaffer, M L Marazita, L M Kaste, G D Slade, R B Fillingim, R Ohrbach, W Maixner, T Kocher, O Bernhardt, A Teumer, C Schwahn, K Sipilä, R Lähdesmäki, M Männikkö, P Pesonen, M Järvelin, C M Rizzatti-Barbosa, C B Meloto, M Ribeiro-Dasilva, L Diatchenko, P Serrano, S B Smith
Temporomandibular disorder (TMD) is a musculoskeletal condition characterized by pain and reduced function in the temporomandibular joint and/or associated masticatory musculature. Prevalence in the United States is 5% and twice as high among women as men. We conducted a discovery genome-wide association study (GWAS) of TMD in 10,153 participants (769 cases, 9,384 controls) of the US Hispanic Community Health Study/Study of Latinos (HCHS/SOL). The most promising single-nucleotide polymorphisms (SNPs) were tested in meta-analysis of 4 independent cohorts...
January 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28076930/hormone-receptor-expression-in-human-fascial-tissue
#9
C Fede, G Albertin, L Petrelli, M M Sfriso, C Biz, R De Caro, C Stecco
Many epidemiologic, clinical, and experimental findings point to sex differences in myofascial pain in view of the fact that adult women tend to have more myofascial problems with respect to men. It is possible that one of the stimuli to sensitization of fascial nociceptors could come from hormonal factors such as estrogen and relaxin, that are involved in extracellular matrix and collagen remodeling and thus contribute to functions of myofascial tissue. Immunohistochemical and molecular investigations (real-time PCR analysis) of relaxin receptor 1 (RXFP1) and estrogen receptor-alpha (ERα) localization were carried out on sample of human fascia collected from 8 volunteers patients during orthopedic surgery (all females, between 42 and 70 yrs, divided into pre- and post-menopausal groups), and in fibroblasts isolated from deep fascia, to examine both protein and RNA expression levels...
November 2, 2016: European Journal of Histochemistry: EJH
https://www.readbyqxmd.com/read/28073832/reperfusion-therapy-with-recombinant-human-relaxin-2-serelaxin-attenuates-myocardial-infarct-size-and-nlrp3-inflammasome-following-ischemia-reperfusion-injury-via-enos-dependent-mechanism
#10
Juan Valle Raleigh, Adolfo G Mauro, Teja Devarakonda, Carlo Marchetti, Jun He, Erica Kim, Scott Filippone, Anindita Das, Stefano Toldo, Antonio Abbate, Fadi N Salloum
AIMS: The preconditioning-like infarct-sparing and anti-inflammatory effects of the peptide hormone relaxin following ischemic injury have been studied in the heart. Whether reperfusion therapy with recombinant human relaxin-2, serelaxin, reduces myocardial infarct size and attenuates the subsequent NLRP3 inflammasome activation leading to further loss of functional myocardium following ischemia/reperfusion (I/R) injury is unknown. METHODS AND RESULTS: After baseline echocardiography, adult male wild-type C57BL or eNOS knockout mice underwent myocardial infarction (MI) by coronary artery ligation for 30 min followed by 24 h reperfusion...
January 10, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28026087/oral-contraceptive-therapy-reduces-serum-relaxin-2-in-elite-female-athletes
#11
Sayaka Nose-Ogura, Osamu Yoshino, Kaori Yamada-Nomoto, Mariko Nakamura, Miyuki Harada, Michiko Dohi, Toru Okuwaki, Yutaka Osuga, Takashi Kawahara, Shigeru Saito
AIM: Recent investigations have demonstrated that athletes with high relaxin-2 levels have a high risk of anterior cruciate ligament injuries, while athletes taking oral contraceptives (OC) have low relaxin-2 levels. It has not yet been clarified whether taking OC reduces relaxin-2 levels. The purpose of this study was to investigate changes in relaxin-2 levels in athletes taking OC. METHODS: Levels of relaxin-2, estradiol, progesterone, luteinizing hormone and follicle-stimulating hormone were measured in serum samples (n = 183) from 106 elite female athletes...
December 27, 2016: Journal of Obstetrics and Gynaecology Research
https://www.readbyqxmd.com/read/28009437/serelaxin-in-clinical-development-past-present-and-future
#12
REVIEW
Elaine Unemori
The availability of highly purified recombinant human relaxin, serelaxin, has enabled the conduct of clinical trials in several indications and the elucidation of its pharmacology in human subjects. These studies have demonstrated that serelaxin has unique hemodynamic properties that likely contribute to organ protection and long-term outcome benefits in acute heart failure. Clinical observations support its consideration for therapeutic use in other patient populations, including those with chronic heart failure, coronary artery disease, portal hypertension and acute renal failure...
December 23, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28004452/inhibitory-mechanism-of-l-glutamic-acid-on-spawning-of-the-starfish-patiria-asterina-pectinifera
#13
Masatoshi Mita
L-Glutamic acid was previously identified as an inhibitor of spawning in the starfish Patiria (Asterina) pectinifera; this study examined how L-glutamic acid works. Oocyte release from ovaries of P. pectinifera occurred after germinal vesicle breakdown (GVBD) and follicular envelope breakdown (FEBD) when gonads were incubated ex vivo with either relaxin-like gonad-stimulating peptide (RGP) or 1-methyladenine (1-MeAde). L-Glutamic acid blocked this spawning phenotype, causing the mature oocytes to remain within the ovaries...
December 22, 2016: Molecular Reproduction and Development
https://www.readbyqxmd.com/read/27933606/relaxin-like-peptides-in-male-reproduction-a-human-perspective
#14
REVIEW
Richard Ivell, Alexander I Agoulnik, Ravinder Anand-Ivell
The relaxin family of peptide hormones and their cognate G-protein coupled receptors are becoming physiologically well characterized in the cardiovascular system and particularly in female reproductive processes. Much less is known about the physiology and pharmacology of these peptides in male reproduction, particularly as regards the human. H2-relaxin is involved in prostate function and growth, while INSL3 is a major product of the testicular Leydig cells and in the adult appears to modulate steroidogenesis and germ cell survival...
December 9, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27928890/identification-of-porcine-relaxin-in-plasma-by-liquid-chromatography-high-resolution-mass-spectrometry
#15
April S Y Wong, Emmie N M Ho, W H Kwok, Gary N W Leung, Yuehong Shen, Robert Z Qi, Samuel K Yue, Terence S M Wan
Relaxin (RLX) has demonstrated diverse pharmacological effects in various scientific and clinical studies. The emergence of porcine relaxin (pRLX) has raised concerns on the doping potential of pRLX. There have also been speculations in the horseracing industry on its covert use. To control the abuse of pRLX in equine sports, a method to detect pRLX effectively and to provide its unequivocal identification in equine biological samples is required. This paper reports on the detection and confirmation of pRLX in equine plasma by liquid chromatography-high resolution mass spectrometry...
December 8, 2016: Drug Testing and Analysis
https://www.readbyqxmd.com/read/27922185/relaxin-family-peptides-structure-activity-relationship-studies
#16
REVIEW
Nitin A Patil, K Johan Rosengren, Frances Separovic, John D Wade, Ross A D Bathgate, Mohammed Akhter Hossain
The human relaxin peptide family consists of seven cystine-rich peptides, four of which are known to signal through relaxin family peptide receptors, RXFP1-4. Considering the vital roles these peptides play in physiology and various diseases, they are of considerable importance for drug discovery and development. Detailed structure-activity relationship (SAR) studies towards understanding the role of important residues in each of these peptides have been reported over the years and utilised for design of antagonists and minimised agonist variants...
December 6, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27905855/reply-promise-and-limitations-of-relaxin-based-therapies-in-chronic-fibrotic-lung-diseases
#17
Jiangning Tan, Daniel J Kass
No abstract text is available yet for this article.
December 1, 2016: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/27905854/promise-and-limitations-of-relaxin-based-therapies-in-chronic-fibrotic-lung-diseases
#18
Simon G Royce, Ross A D Bathgate, Chrishan S Samuel
No abstract text is available yet for this article.
December 1, 2016: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/27888281/the-actions-of-relaxin-family-peptides-on-signal-transduction-pathways-activated-by-the-relaxin-family-peptide-receptor-rxfp4
#19
Sheng Y Ang, Dana S Hutchinson, Bronwyn A Evans, Mohammed A Hossain, Nitin Patil, Ross A D Bathgate, Martina Kocan, Roger J Summers
The relaxin family peptide receptor 4 (RXFP4) is a G protein-coupled receptor (GPCR) expressed in the colorectum with emerging roles in metabolism and appetite regulation. It is activated by its cognate ligand insulin-like peptide 5 (INSL5) that is expressed in enteroendocrine L cells in the gut. Whether other evolutionarily related peptides such as relaxin-2, relaxin-3, or INSL3 activate RXFP4 signal transduction mechanisms with a pattern similar to or distinct from INSL5 is still unclear. In this study, we compare the signaling pathways activated by various relaxin family peptides to INSL5...
January 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/27864846/monochorial-diamniotic-dizygotic-twins-in-a-german-shepherd-dog-a-case-report
#20
C Urhausen, K Wolf, A Beineke, C Dierks, M Schmicke, A Einspanier, A R Günzel-Apel
A 6.5-year-old clinically healthy German Shepherd Dog with regular oestrous cycles of 6 months was presented for pregnancy diagnosis on day 38 after ovulation (p.ov.). Ultrasonography revealed three individual placental sites in progressed resorption and two vital adequately developed foetuses sharing a joint placenta. On days 41 and 48 p.ov., sonographic signs indicated normal development of both foetuses, but on day 52 p.ov., both foetuses were found to be dead. A caesarean section was performed the same day...
November 18, 2016: Reproduction in Domestic Animals, Zuchthygiene
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