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https://www.readbyqxmd.com/read/28102934/crosstalk-between-angiotensin-and-the-non-amyloidogenic-pathway-of-alzheimer-s-amyloid-precursor-protein
#1
Anna Maria Kanarek, Annika Wagner, Jim Küppers, Michael Gütschow, Rolf Postina, Elzbieta Kojro
The association between hypertension and an increased risk for Alzheimer's disease (AD) and dementia is well established. Many data suggest that modulation of the renin-angiotensin system may be meaningful for the prevention and therapy of neurodegenerative disorders, in particular AD. Proteolytic cleavage of the amyloid precursor protein (APP) by α-secretase precludes formation of neurotoxic Aβ peptides and is expected to counteract the development of AD. An established approach for the up-regulation of α-secretase cleavage is activation of G protein-coupled receptors (GPCRs)...
January 19, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28102227/singular-location-and-signaling-profile-of-adenosine-a2a-cannabinoid-cb1-receptor-heteromers-in-the-dorsal-striatum
#2
Estefanía Moreno, Anna Chiarlone, Mireia Medrano, Mar Puigdellívol, Lucka Bibic, Lesley A Howell, Eva Resel, Nagore Puente, María J Casarejos, Juan Perucho, Joaquín Botta, Nuria Suelves, Francisco Ciruela, Silvia Ginés, Ismael Galve-Roperh, Vicent Casadó, Pedro Grandes, Beat Lutz, Krisztina Monory, Enric I Canela, Carmen Lluís, Peter J McCormick, Manuel Guzmán
The dorsal striatum is a key node for many neurobiological processes such as motor activity, cognitive functions, and affective processes. The proper functioning of striatal neurons relies critically on metabotropic receptors. Specifically, the main adenosine and endocannabinoid receptors present in the striatum, ie, adenosine A2A receptor (A2AR) and cannabinoid CB1 receptor (CB1R), are of pivotal importance in the control of neuronal excitability. Facilitatory and inhibitory functional interactions between striatal A2AR and CB1R have been reported, and evidence supports that this cross-talk may rely, at least in part, on the formation of A2AR-CB1R heteromeric complexes...
January 19, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28102109/epigenetic-regulation-of-rgs2-regulator-of-g-protein-signaling-2-in-chemoresistant-ovarian-cancer-cells
#3
Ercan Cacan
Regulator of G-protein signaling 2 (RGS2) is a GTPase-activating protein functioning as an inhibitor of G-protein coupled receptors (GPCRs). RGS2 dysregulation was implicated in solid tumour development and RGS2 downregulation has been reported in prostate and ovarian cancer progression. However, the molecular mechanism by which RGS2 expression is suppressed in ovarian cancer remains unknown. The expression and epigenetic regulation of RGS2 in chemosensitive and chemoresistant ovarian cancer cells were determined by qRT-PCR and chromatin immunoprecipitation assays, respectively...
January 19, 2017: Journal of Chemotherapy
https://www.readbyqxmd.com/read/28101188/mir-125a-3p-targetedly-regulates-git1-expression-to-inhibit-osteoblastic-proliferation-and-differentiation
#4
Xiao-Mei Tu, Yang-Lin Gu, Guo-Qin Ren
Osteoblasts are a prerequisite for osteogenesis and bone formation, and play a key role in metabolic balance, growth, development and wound repair. G protein-coupled receptor kinase interacting protein 1 (GIT1) and a series of miRNAs are known to have important effects in the growth and migration of osteoblasts, but little is known about micro RNAs (miRNAs) targeting GIT1. The present study found that miR-125a-3p has matching sites on GIT1. In the osteoblastic differentiation process of human bone marrow-derived mesenchymal stem cells (HMSCs), the expression of miR-125a-3p was suppressed compared with that in non-differentiating (HMSCs) while the expression of GIT1 showed a gradual and significant increase...
December 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28100777/structure-activity-relationship-of-%C3%AE-mating-pheromone-from-the-fungal-pathogen-fusarium-oxysporum
#5
Stefania Vitale, Angélica Partida-Hanon, Soraya Serrano, Álvaro Martínez-Del-Pozo, Antonio Di Pietro, David Turrà, Marta Bruix
During sexual development, ascomycete fungi produce two types of peptide pheromones termed a and α. The α pheromone from the budding yeast Saccharomyces cerevisiae, a thirteen residue peptide which elicits cell cycle arrest and chemotropic growth, has served as paradigm for the interaction of small peptides with their cognate G protein-coupled receptors (GPCRs). However, no structural information is currently available for α pheromones from filamentous ascomycetes, which are significantly shorter and share almost no sequence similarity with the S...
January 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28100643/fluid-shear-stress-increases-transepithelial-transport-of-ca2-in-ciliated-distal-convoluted-and-connecting-tubule-cells
#6
Sami G Mohammed, Francisco J Arjona, Femke Latta, René J M Bindels, Ronald Roepman, Joost G J Hoenderop
In kidney, transcellular transport of Ca(2+) is mediated by transient receptor potential vanilloid 5 and Na(+)-Ca(2+) exchanger 1 proteins in distal convoluted and connecting tubules (DCT and CNT, respectively). It is not yet understood how DCT/CNT cells can adapt to differences in tubular flow rate and, consequently, Ca(2+) load. This study aims to elucidate the molecular mechanisms by which DCT/CNT cells sense fluid dynamics to control transepithelial Ca(2+) reabsorption and whether their primary cilia play an active role in this process...
January 18, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28100502/rack1-regulates-angiotensin-ii-induced-contractions-of-shr-preglomerular-vascular-smooth-muscle-cells
#7
Xiao Zhu, Edwin K Jackson
The preglomerular microcirculation of spontaneously hypertensive rats (SHR) is hypersensitive to angiotensin II, and studies show that this is likely due to enhanced convergent signaling between G-protein subunits αq (Gαq; released by angiotensin II) and G-protein subunits βγ (Gβγ; released by Gi-coupled receptors) to active phospholipase C (PLC). Here we investigated the molecular basis for the enhanced convergent signaling between Gβγ and Gαq in SHR preglomerular vascular smooth muscle cells (PGVSMCs)...
January 18, 2017: American Journal of Physiology. Renal Physiology
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
#8
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
#9
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/28098235/molecular-characterization-of-pediatric-restrictive-cardiomyopathy-from-integrative-genomics
#10
Tara N Rindler, Robert B Hinton, Nathan Salomonis, Stephanie M Ware
Pediatric restrictive cardiomyopathy (RCM) is a genetically heterogeneous heart disease with limited therapeutic options. RCM cases are largely idiopathic; however, even within families with a known genetic cause for cardiomyopathy, there is striking variability in disease severity. Although accumulating evidence implicates both gene expression and alternative splicing in development of dilated cardiomyopathy (DCM), there have been no detailed molecular characterizations of underlying pathways dysregulated in RCM...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28096479/igf-1-receptor-modulates-foxo1-mediated-tamoxifen-response-in-breast-cancer-cells
#11
Ali Vaziri-Gohar, Yan Zheng, Kevin D Houston
: Tamoxifen is a common adjuvant treatment for ERalpha-positive breast cancer patients, however acquired resistance abrogates the efficacy of this therapeutic approach. We recently demonstrated that G protein-coupled estrogen receptor 1 (GPER1) mediates tamoxifen action in breast cancer cells by inducing insulin-like growth factor binding protein-1 (IGFBP-1) to inhibit IGF-1-dependent signaling. To determine if dysregulation of IGFBP-1 induction is associated with tamoxifen resistance, IGFBP-1 transcription was measured in tamoxifen-resistant MCF-7 cells (TamR) after tamoxifen (Tam) treatment...
January 17, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28096465/sequences-within-the-c-terminus-of-the-metabotropic-glutamate-receptor-mglur5-are-responsible-for-inner-nuclear-membrane-localization
#12
Ismail Sergin, Yuh-Jiin I Jong, Steven K Harmon, Vikas Kumar, Karen L O'Malley
Traditionally G-protein coupled receptors (GPCR) are thought to be located on the cell surface where they transmit extracellular signals to the cytoplasm. However recent studies indicate that some GPCRs are also localized to various subcellular compartments such as the nucleus where they appear required for various biological functions. For example, the metabotropic glutamate receptor 5, mGluR5, is concentrated at the inner nuclear membrane (INM) where it mediates Ca2+ changes in the nucleoplasm by coupling with Gq/11...
January 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28096461/differential-contribution-of-transmembrane-domains-iv-v-vi-and-vii-to-human-angiotensin-ii-type-1-receptor-homomer-formation
#13
Brent M Young, Elaine Nguyen, Matthew A J Chedrawe, Jan K Rainey, Denis J Dupré
G protein-coupled receptors (GPCRs) play an important role in drug therapy, and represent one of the largest families of drug targets. The angiotensin II type 1 receptor (AT1R) is notable as it has a central role in the treatment of cardiovascular disease. Blockade of AT1R signaling has been shown to alleviate hypertension and improve outcomes in patients with heart failure. Despite this, it has become apparent that our initial understanding of AT1R signaling is over-simplified. There is considerable evidence to suggest that AT1R signaling is highly modified in the presence of receptor-receptor interactions, but there is very little structural data available to explain this phenomenon even with the recent elucidation of the AT1R crystal structure...
January 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28096187/gprasp2-a-novel-causative-gene-mutated-in-an-x-linked-recessive-syndromic-hearing-loss
#14
Guangqian Xing, Jun Yao, Chunyu Liu, Qinjun Wei, Xuli Qian, Lingxin Wu, Yajie Lu, Xin Cao
BACKGROUND: A substantial amount of nuclear genes have been identified to be implicated in genetic hearing loss, while X-linked hearing loss is genetically heterogeneous and relatively infrequent. OBJECTIVE: To identify the causative gene mutation in a five-generation Chinese family with an X-linked recessive syndromic hearing loss (SHL). METHODS: Targeted X-chromosome exome sequencing was conducted, and cosegregation analysis was performed in the members of the affected family...
January 17, 2017: Journal of Medical Genetics
https://www.readbyqxmd.com/read/28094956/radiolabeled-r954-derivatives-for-imaging-bradykinin-b1-receptor-expression-with-positron-emission-tomography
#15
Hsiou-Ting Kuo, Jinhe Pan, Joseph Lau, Chengcheng Zhang, Jutta Zeisler, Nadine Colpo, Francois Benard, Kuo-Shyan Lin
Peptide receptors have emerged as promising targets for diagnosis and therapy. The aberrant overexpression of these receptors in different cancer subtypes allows for the adoption of new treatment strategies that complement conventional chemotherapies. Bradykinin B1 receptor (B1R) is a G protein-coupled receptor that is overexpressed in many cancers, with limited expression in healthy tissues. Previously, we developed 68Ga- and 18F-labeled derivatives of B1R antagonist peptides B9858 and B9958, and successfully targeted B1R-expressing tumor xenografts in vivo...
January 17, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28094002/the-rfamide-receptor-dmsr-1-regulates-stress-induced-sleep-in-c-elegans
#16
Michael J Iannacone, Isabel Beets, Lindsey E Lopes, Matthew A Churgin, Christopher Fang-Yen, Matthew D Nelson, Liliane Schoofs, David M Raizen
In response to environments that cause cellular stress, animals engage in sleep behavior that facilitates recovery from the stress. In Caenorhabditis elegans, stress-induced sleep(SIS) is regulated by cytokine activation of the ALA neuron, which releases FLP-13 neuropeptides characterized by an amidated arginine-phenylalanine (RFamide) C-terminus motif. By performing an unbiased genetic screen for mutants that impair the somnogenic effects of FLP-13 neuropeptides, we identified the gene dmsr-1, which encodes a G-protein coupled receptor similar to an insect RFamide receptor...
January 17, 2017: ELife
https://www.readbyqxmd.com/read/28093215/melanocortin-4-receptor-constitutive-activity-inhibits-l-type-voltage-gated-calcium-channels-in-neurons
#17
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 13, 2017: Neuroscience
https://www.readbyqxmd.com/read/28091904/effects-of-release-active-antibodies-to-cd4-receptor-on-the-level-of-lck-kinase-in-cultured-mononuclear-cells-from-human-peripheral-blood
#18
A G Emel'yanova, V V Grechenko, N V Petrova, I P Shilovskii, E A Gorbunov, S A Tarasov, M R Khaitov, S G Morozov, O I Epshtein
For evaluation of effects of release-active antibodies to CD4 on cultured lymphocytes from human peripheral blood, we measured intracellular content of lck-kinase cell-based ELISA. In cells treated with release-active antibodies to CD4, the content of intracellular lck-kinase significantly (p<0.01) decreased in comparison with the control (purified water processed in a similar way). Phytohemagglutinin had no effect on the concentration of lck-kinase in cells. The decrease in the content of CD4-associated lck protein suggests that the preparation enhanced intracellular coupling of lck-kinase with T-cell receptor and potentiated T-cell immune response...
January 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28091894/mechanisms-of-action-of-surgical-interventions-on-weight-related-diseases-the-potential-role-of-bile-acids
#19
REVIEW
Mohsen Mazidi, Pedro Paulo P de Caravatto, John R Speakman, Ricardo V Cohen
Surgical interventions for weight-related diseases (SWRD) may have substantial and sustainable effect on weight reduction, also leading to a higher remission rate of type 2 diabetes (T2D) mellitus than any other medical treatment or lifestyle intervention. The resolution of T2D after Roux-en-Y gastric bypass (RYGB) typically occurs too quickly to be accounted for by weight loss alone, suggesting that these operations have a direct impact on glucose homeostasis. The mechanisms underlying these beneficial effects however remain unclear...
January 14, 2017: Obesity Surgery
https://www.readbyqxmd.com/read/28091608/binding-of-n-methylscopolamine-to-the-extracellular-domain-of-muscarinic-acetylcholine-receptors
#20
Jan Jakubík, Alena Randáková, Pavel Zimčík, Esam E El-Fakahany, Vladimír Doležal
Interaction of orthosteric ligands with extracellular domain was described at several aminergic G protein-coupled receptors, including muscarinic acetylcholine receptors. The orthosteric antagonists quinuclidinyl benzilate (QNB) and N-methylscopolamine (NMS) bind to the binding pocket of the muscarinic acetylcholine receptor formed by transmembrane α-helices. We show that high concentrations of either QNB or NMS slow down dissociation of their radiolabeled species from all five subtypes of muscarinic acetylcholine receptors, suggesting allosteric binding...
January 16, 2017: Scientific Reports
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