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https://www.readbyqxmd.com/read/28912066/the-camp-effectors-pka-and-epac-activate-endothelial-no-synthase-through-pi3k-akt-pathway-in-human-endothelial-cells
#1
Verónica García-Morales, María Luaces-Regueira, Manuel Campos-Toimil
3',5'-cyclic adenosine monophosphate (cAMP) exerts an endothelium-dependent vasorelaxant action by stimulating endothelial NO synthase (eNOS) activity, and the subsequent NO release, through cAMP protein kinase (PKA) and exchange protein directly activated by cAMP (Epac) activation in endothelial cells. We have here investigated the mechanism by which the cAMP-Epac/PKA pathway activates eNOS. cAMP-elevating agents (forskolin and dibutyryl-cAMP) and the joint activation of PKA (6-Bnz-cAMP) and Epac (8-pCPT-2'-O-Me-cAMP) increased cytoplasmic Ca(2+) concentration ([Ca(2+)]c) in ≤ 30% of fura-2-loaded isolated human umbilical vein endothelial cells (HUVEC)...
September 11, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28877931/prostaglandin-e2-inhibits-histamine-evoked-ca2-release-in-human-aortic-smooth-muscle-cells-through-hyperactive-camp-signalling-junctions-and-protein-kinase-a
#2
Emily J A Taylor, Evangelia Pantazaka, Kathryn L Shelley, Colin W Taylor
In human aortic smooth muscle cells (ASMC), prostaglandin E2 (PGE2) stimulates adenylyl cyclase (AC) and attenuates the increase in intracellular free Ca(2+) concentration ([Ca(2+)]i) evoked by activation of histamine H1 receptors. The mechanisms are not resolved. We show that cAMP mediates inhibition of histamine-evoked Ca(2+) signals by PGE2 Exchange proteins activated by cAMP (EPACs) were not required, but the effects were attenuated by inhibition of cAMP-dependent protein kinase (PKA). PGE2 had no effect on the Ca(2+) signals evoked by protease-activated receptors, heterologously expressed muscarinic M3 receptors, or by direct activation of inositol 1,4,5-trisphosphate (IP3) receptors by photolysis of caged IP3 The rate of Ca(2+) removal from the cytosol was unaffected by PGE2, but PGE2 attenuated histamine-evoked IP3 accumulation...
September 6, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28864549/atrial-natriuretic-peptide-anp-affects-stimulus-secretion-coupling-of-pancreatic-%C3%AE-cells
#3
Sabrina Undank, Julia Kaiser, Jelena Sikimic, Martina Düfer, Peter Krippeit-Drews, Gisela Drews
ANP influences glucose homeostasis and possibly acts as a link between the cardiovascular system and metabolism, especially in metabolic disorders like diabetes. The present study aimed to evaluate effects of ANP on β-cell function by the use of a β-cell specific knockout of the ANP receptor with guanylate cyclase activity (βGC-A-KO). ANP augmented insulin secretion at the threshold glucose concentration of 6 mM and decreased KATP single channel activity in β-cells of control mice but not of βGC-A-KO mice...
September 1, 2017: Diabetes
https://www.readbyqxmd.com/read/28864467/upregulation-of-epac-1-in-hepatic-stellate-cells-by-prostaglandin-e2-in-liver-fibrosis-is-associated-with-reduced-fibrogenesis
#4
Marlies Schippers, Leonie Beljaars, Eduard Post, Sophie Lotersztajn, Catharina Reker-Smit, Bing Han, Pablo A Llancao, Martina Schmidt, Klaas Poelstra
Exchange protein activated by cAMP (Epac-1) is an important signaling mechanism for cAMP-mediated effects but factors that change Epac-1 levels are unknown. Such factors are relevant because it has been postulated that Epac-1 directly affects fibrogenesis. Prostaglandin E2 (PGE2) is a well-known cAMP-activator and we therefore studied the effects of this cyclo-oxygenase product on Epac-1 expression and on fibrogenesis within the liver. Liver fibrosis was induced by 8 weeks CCL4 administration to mice. In the last 2 weeks, mice received vehicle, PGE2, COX-2 inhibitor Niflumic acid (NFA), or PGE2 coupled to cell-specific carriers to hepatocytes, Kupffer cells or hepatic stellate cells (HSC)...
September 1, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28851815/epac-rap1-axis-mediated-switch-in-the-response-of-primary-and-metastatic-melanoma-to-cyclic-amp
#5
Carlos I Rodriguez, Edgardo Castro-Perez, Kirthana Prabhakar, Laura Block, B Jack Longley, Jaclyn A Wisinski, Michelle E Kimple, Vijayasaradhi Setaluri
Cyclic AMP (cAMP) is an important second messenger that regulates a wide range of physiological processes. In mammalian cutaneous melanocytes, cAMP-mediated signaling pathways activated by G-protein coupled receptors (GPCRs), like melanocortin 1 receptor (MC1R), play critical roles in melanocyte homeostasis including cell survival, proliferation and pigment synthesis. Impaired cAMP signaling is associated with increased risk of cutaneous melanoma. Whereas mutations in mitogen activated protein kinase (MAPK) pathway components are the most frequent oncogenic drivers of melanoma, the role of cAMP in melanoma is not well understood...
August 29, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28759570/camp-dependent-activation-of-protein-kinase-a-attenuates-respiratory-syncytial-virus-induced-human-airway-epithelial-barrier-disruption
#6
Fariba Rezaee, Terri J Harford, Debra T Linfield, Ghaith Altawallbeh, Ronald J Midura, Andrei I Ivanov, Giovanni Piedimonte
Airway epithelium forms a barrier to the outside world and has a crucial role in susceptibility to viral infections. Cyclic adenosine monophosphate (cAMP) is an important second messenger acting via two intracellular signaling molecules: protein kinase A (PKA) and the guanidine nucleotide exchange factor, Epac. We sought to investigate effects of increased cAMP level on the disruption of model airway epithelial barrier caused by RSV infection and the molecular mechanisms underlying cAMP actions. Human bronchial epithelial cells were infected with RSV-A2 and treated with either cAMP releasing agent, forskolin, or cAMP analogs...
2017: PloS One
https://www.readbyqxmd.com/read/28742159/%C3%AE-adrenergic-signaling-broadly-contributes-to-ltp-induction
#7
Joanna Jȩdrzejewska-Szmek, Vincent Luczak, Ted Abel, Kim T Blackwell
Long-lasting forms of long-term potentiation (LTP) represent one of the major cellular mechanisms underlying learning and memory. One of the fundamental questions in the field of LTP is why different molecules are critical for long-lasting forms of LTP induced by diverse experimental protocols. Further complexity stems from spatial aspects of signaling networks, such that some molecules function in the dendrite and some are critical in the spine. We investigated whether the diverse experimental evidence can be unified by creating a spatial, mechanistic model of multiple signaling pathways in hippocampal CA1 neurons...
July 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28740152/a-cell-based-quantitative-and-isoform-specific-assay-for-exchange-proteins-directly-activated-by-camp
#8
Yingmin Zhu, Fang Mei, Pei Luo, Xiaodong Cheng
Extensive functional studies of the exchange protein directly activated by cAMP (EPAC) family of signaling molecules have demonstrated that EPAC proteins play a fundamental role in several physiological and pathophysiological responses, therefore are attractive drug targets. In this report, the development of a cell-based, medium to high throughput screening assay that is capable of monitoring EPAC-mediated activation of cellular Rap1 in an isoform-specific manner is described. This assay adapts a conventional ELISA format with immobilized RalGDS-RBD as a bait to selectively capture GTP-bound active Rap1...
July 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28731505/calcium-calmodulin-dependent-kinase-2-mediates-epac-induced-spontaneous-transient-outward-currents-in-rat-vascular-smooth-muscle
#9
Edward S A Humphries, Tomoko Kamishima, John M Quayle, Caroline Dart
KEY POINTS: The Ca(2+) and redox-sensing enzyme Ca(2+) /calmodulin-dependent kinase 2 (CaMKII) is a crucial and well-established signalling molecule in the heart and brain. In vascular smooth muscle, which controls blood flow by contracting and relaxing in response to complex Ca(2+) signals and oxidative stress, surprisingly little is known about the role of CaMKII. The vasodilator-induced second messenger cAMP can relax vascular smooth muscle via its effector, exchange protein directly activated by cAMP (Epac), by activating spontaneous transient outward currents (STOCs) that hyperpolarize the cell membrane and reduce voltage-dependent Ca(2+) influx...
September 15, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28713274/stimulation-of-adenosine-a2b-receptor-inhibits-endothelin-1-induced-cardiac-fibroblast-proliferation-and-%C3%AE-smooth-muscle-actin-synthesis-through-the-camp-epac-pi3k-akt-signaling-pathway
#10
Sarawuth Phosri, Ajaree Arieyawong, Kwanchai Bunrukchai, Warisara Parichatikanond, Akiyuki Nishimura, Motohiro Nishida, Supachoke Mangmool
Background and Purpose: Cardiac fibrosis is characterized by an increase in fibroblast proliferation, overproduction of extracellular matrix proteins, and the formation of myofibroblast that express α-smooth muscle actin (α-SMA). Endothelin-1 (ET-1) is involved in the pathogenesis of cardiac fibrosis. Overstimulation of endothelin receptors induced cell proliferation, collagen synthesis, and α-SMA expression in cardiac fibroblasts. Although adenosine was shown to have cardioprotective effects, the molecular mechanisms by which adenosine A2 receptor inhibit ET-1-induced fibroblast proliferation and α-SMA expression in cardiac fibroblasts are not clearly identified...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28689685/-home-and-recreational-injuries-in-children-under-1year-10years-of-experience
#11
B Lacarra, S Guyet-Job, G Pédrono, M A Le Rouzic, D Dufour, B Thélot, P Le Roux
BACKGROUND: There is little research on the prevalence and characteristics of home and recreational injuries in infants under 12months of age. However, domestic accidents result in an average of 50 infant deaths in France every year. METHODS: A descriptive and retrospective study was conducted, based on data from the permanent investigation on home and recreational injuries in infants under 12months of age (EPAC) published by the Institute for Public Health. Data were collected from 2004 to 2013 in the pediatric emergency department of Le Havre hospital...
July 6, 2017: Archives de Pédiatrie: Organe Officiel de la Sociéte Française de Pédiatrie
https://www.readbyqxmd.com/read/28679628/recruitment-of-epac2a-to-insulin-granule-docking-sites-regulates-priming-for-exocytosis
#12
Ida Alenkvist, Nikhil R Gandasi, Sebastian Barg, Anders Tengholm
Epac is a cAMP-activated guanine nucleotide exchange factor that mediates cAMP signaling in various types of cells, including β-cells, where it is involved in the control of insulin secretion. Upon activation, the protein redistributes to the plasma membrane but the underlying molecular mechanisms and functional consequences are unclear. Using quantitative high-resolution microscopy we found that cAMP elevation caused rapid binding of Epac2A to the β-cell plasma membrane, where it accumulated specifically at secretory granules and rendered them more prone to undergo exocytosis...
July 5, 2017: Diabetes
https://www.readbyqxmd.com/read/28634298/analyses-of-pde-regulated-phosphoproteomes-reveal-unique-and-specific-camp-signaling-modules-in-t-cells
#13
Michael-Claude G Beltejar, Ho-Tak Lau, Martin G Golkowski, Shao-En Ong, Joseph A Beavo
Specific functions for different cyclic nucleotide phosphodiesterases (PDEs) have not yet been identified in most cell types. Conventional approaches to study PDE function typically rely on measurements of global cAMP, general increases in cAMP-dependent protein kinase (PKA), or the activity of exchange protein activated by cAMP (EPAC). Although newer approaches using subcellularly targeted FRET reporter sensors have helped define more compartmentalized regulation of cAMP, PKA, and EPAC, they have limited ability to link this regulation to downstream effector molecules and biological functions...
July 25, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28632993/the-role-of-small-gtpases-and-epac-rap-signaling-in-the-regulation-of-the-blood-brain-and-blood-retinal-barriers
#14
Carla J Ramos, David A Antonetti
Maintenance and regulation of the vascular endothelial cell junctional complex is critical for proper barrier function of the blood-brain barrier (BBB) and the highly related blood-retinal barrier (BRB) that help maintain proper neuronal environment. Recent research has demonstrated that the junctional complex is actively maintained and can be dynamically regulated. Studies focusing on the mechanisms of barrier formation, maintenance, and barrier disruption have been of interest to understanding development of the BBB and BRB and identifying a means for therapeutic intervention for diseases ranging from brain tumors and dementia to blinding eye diseases...
July 3, 2017: Tissue Barriers
https://www.readbyqxmd.com/read/28629760/cardiac-overexpression-of-epac1-in-transgenic-mice-rescues-lipopolysaccharide-induced-cardiac-dysfunction-and-inhibits-jak-stat-pathway
#15
Huiling Jin, Takayuki Fujita, Meihua Jin, Reiko Kurotani, Iyuki Namekata, Shogo Hamaguchi, Yuko Hidaka, Wenqian Cai, Kenji Suita, Yoshiki Ohnuki, Yasumasa Mototani, Kouichi Shiozawa, Rajesh Prajapati, Chen Liang, Masanari Umemura, Utako Yokoyama, Motohiko Sato, Hikaru Tanaka, Satoshi Okumura, Yoshihiro Ishikawa
Pro-inflammatory cytokines are released in septic shock and impair cardiac function via the Jak-STAT pathway. It is well known that sympathetic stimulation leads to coupling of the β-adrenergic receptor/Gs/adenylyl cyclase, a membrane-bound enzyme that catalyzes the conversion of ATP to cAMP, thereby stimulating protein kinase A (PKA) and ultimately compensating for cardiac dysfunction. The mechanism of such compensation by catecholamine has been traditionally understood as PKA-mediated enforcement of cardiac contractility...
June 16, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28589946/elevated-prostaglandin-e2-post-bone-marrow-transplant-mediates-interleukin-1%C3%AE-related-lung-injury
#16
G J Martínez-Colón, Q M Taylor, C A Wilke, A B Podsiad, B B Moore
Hematopoietic stem cell transplant (HSCT) treats or cures a variety of hematological and inherited disorders. Unfortunately, patients who undergo HSCT are susceptible to infections by a wide array of opportunistic pathogens. Pseudomonas aeruginosa bacteria can have life-threatening effects in HSCT patients by causing lung pathology that has been linked to high levels of the potent pro-inflammatory cytokine, interleukin-1β (IL-1β). Using a murine bone marrow transplant (BMT) model, we show that overexpression of prostaglandin E2 (PGE2) post-BMT signals via EP2 or EP4 to induce cyclic adenosine monophosphate (cAMP), which activates protein kinase A or the exchange protein activated by cAMP (Epac) to induce cAMP response element binding-dependent transcription of IL-1β leading to exacerbated lung injury in BMT mice...
June 7, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28580839/-express-epac-and-nociceptor-sensitization
#17
Li-Yen Huang, Yanping Gu
No abstract text is available yet for this article.
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28558129/somatostatin-depresses-the-excitability-of-subicular-bursting-cells-roles-of-inward-rectifier-k-channels-kcnq-channels-and-epac
#18
Binqi Hu, Nicholas I Cilz, Saobo Lei
The hippocampus is a crucial component for cognitive and emotional processing. The subiculum provides much of the output for this structure but the modulation and function of this region is surprisingly under-studied. The neuromodulator somatostatin (SST) interacts with five subtypes of SST receptors (sst1 to sst5 ) and each of these SST receptor subtypes is coupled to Gi proteins resulting in inhibition of adenylyl cyclase (AC) and decreased level of intracellular cAMP. SST modulates many physiological functions including cognition, emotion, autonomic responses and locomotion...
September 2017: Hippocampus
https://www.readbyqxmd.com/read/28533546/prostaglandin-e2-inhibits-matrix-mineralization-by-human-bone-marrow-stromal-cell-derived-osteoblasts-via-epac-dependent-camp-signaling
#19
Ali Mirsaidi, André N Tiaden, Peter J Richards
The osteoinductive properties of prostaglandin E2 (PGE2) and its signaling pathways have led to suggestions that it may serve as a potential therapeutic strategy for bone loss. However, the prominence of PGE2 as an inducer of bone formation is attributed primarily to findings from studies using rodent models. In the current study, we investigated the effects of PGE2 on human bone marrow stromal cell (hBMSC) lineage commitment and determined its mode of action. We demonstrated that PGE2 treatment of hBMSCs significantly altered the expression profile of several genes associated with osteoblast differentiation (RUNX2 and ALP) and maturation (BGLAP and MGP)...
May 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28512254/catecholamines-facilitate-vegf-dependent-angiogenesis-via-%C3%AE-2-adrenoceptor-induced-epac1-and-pka-activation
#20
Jaspal Garg, Yu-Xi Feng, Sepp R Jansen, Julian Friedrich, Frank Lezoualc'h, Martina Schmidt, Thomas Wieland
Chronic stress has been associated with the progression of cancer and antagonists for β-adrenoceptors (βAR) are regarded as therapeutic option. As they are also used to treat hemangiomas as well as retinopathy of prematurity, a role of endothelial β2AR in angiogenesis can be envisioned. We therefore investigated the role of β2AR-induced cAMP formation by analyzing the role of the cAMP effector molecules exchange factor directly activated by cAMP 1 (Epac1) and protein kinase A (PKA) in endothelial cells (EC)...
July 4, 2017: Oncotarget
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