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Adenylyl cyclases

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https://www.readbyqxmd.com/read/27908592/activation-of-gpr30-stimulates-gtp-binding-of-g%C3%AE-i1-protein-to-sustain-activation-of-erk1-2-in-inhibition-of-prostate-cancer-cell-growth-and-modulates-metastatic-properties
#1
Lau Kin-Mang, Ma Fanny Man-Ting, Xia Jenny Tian, Chan Queeny Kwan Yi, Ng Chi-Fai, To Ka-Fai
Previously, we reported that GPR30 activation by the receptor-specific, non-estrogenic ligand G-1 inhibited in vitro and in vivo growth of prostate cancer (PCa) cells via sustained Erk1/2 activation. Mechanism underlying the sustained Erk1/2 activation for PCa cell growth inhibition remains unclear. Here we report that G-1, through GPR30, activated Gαi1 proteins to sustain Erk1/2 activation but failed to activate adenylyl cyclase (AC) for cAMP production in PCa cells. The chemical-induced activation of AC-cAMP-PKA signaling attenuated Erk1/2 activity and blocked the cell growth inhibitory effects of G-1...
November 28, 2016: Experimental Cell Research
https://www.readbyqxmd.com/read/27904901/effect-of-ticagrelor-on-endothelial-calcium-signalling-and-barrier-function
#2
Dursun Gündüz, Christian Tanislav, Klaus-Dieter Schlüter, Rainer Schulz, Christian Hamm, Muhammad Aslam
The P2Y12 receptor is a Gi-coupled receptor whose activation inhibits adenylyl cyclase and thereby reduces the concentration of intracellular cAMP. Here the hypothesis was tested whether AR-C 66096 or ticagrelor, two direct-acting and reversibly binding P2Y12 receptor antagonists, protect endothelial cell (EC) barrier function by raising intracellular cAMP in ECs. The study was carried out on primary human umbilical vein ECs (HUVECs) and human pulmonary microvascular ECs (hPMECs). AR-C66096 (10 µM) induced a 50 % increase in cAMP in ECs whereas ticagrelor (2-10 µM) had no effect...
December 1, 2016: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/27901486/triple-negative-breast-cancer-development-can-be-selectively-suppressed-by-sustaining-an-elevated-level-of-cellular-cyclic-amp-through-simultaneously-blocking-its-efflux-and-decomposition
#3
Wei Wang, Yue Li, Jessica Y Zhu, Dongdong Fang, Han-Fei Ding, Zheng Dong, Qing Jing, Shi-Bing Su, Shuang Huang
Triple negative breast cancer (TNBC) has the highest mortality among all breast cancer types and lack of targeted therapy is a key factor contributing to its high mortality rate. In this study, we show that 8-bromo-cAMP, a cyclic adenosine monophosphate (cAMP) analog at high concentration (> 1 mM) selectively suppresses TNBC cell growth. However, commonly-used cAMP-elevating agents such as adenylyl cyclase activator forskolin and pan phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) are ineffective...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27900607/mammalian-nucleotidyl-cyclases-and-their-nucleotide-binding-sites
#4
Stefan Dove
Mammalian membranous and soluble adenylyl cyclases (mAC, sAC) and soluble guanylyl cyclases (sGC) generate cAMP and cGMP from ATP and GTP, respectively, as substrates. mACs (nine human isoenzymes), sAC, and sGC differ in their overall structures owing to specific membrane-spanning and regulatory domains but consist of two similarly folded catalytic domains C1 and C2 with high structure-based homology between the cyclase species. Comparison of available crystal structures - VC1:IIC2 (a construct of domains C1a from dog mAC5 and C2a from rat mAC2), human sAC and sGC, mostly in complex with substrates, substrate analogs, inhibitors, metal ions, and/or modulators - reveals that especially the nucleotide binding sites are closely related...
November 30, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27891679/adenylyl-cyclase-3-adenylyl-cyclase-associated-protein-1-cap1-complex-mediates-the-anti-migratory-effect-of-forskolin-in-pancreatic-cancer-cells
#5
Sierra Quinn, Sarai Graves, Clayton Dains-McGahee, Emilee Friedman, Humma Hassan, Piotr Witkowski, Maria E Sabbatini
Pancreatic cancer is one of the most lethal human malignancies. A better understanding of the intracellular mechanism of migration and invasion is urgently needed to develop treatment that will suppress metastases and improve overall survival. Cyclic adenosine monophosphate (cyclic AMP) is a second messenger that has shown to regulate migration and invasion of pancreatic cancer cells. The rise of cyclic AMP suppressed migration and invasion of pancreatic ductal adenocarcinoma cells. Cyclic AMP is formed from cytosolic ATP by the enzyme adenylyl cyclase (AC)...
November 27, 2016: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/27889175/inhibition-of-adenylyl-cyclase-in-the-spinal-cord-alleviates-painful-diabetic-neuropathy-in-zucker-diabetic-fatty-rats
#6
Hao Feng, Guodong Lu, Qingsong Li, Zhonghao Liu
OBJECTIVES: Diabetic neuropathy is the most common complication of both type 1 and type 2 diabetes. In this study, we tested the hypotheses that impaired Gi protein expression/function in the spinal cord is associated with the development of painful neuropathy in people with type 2 diabetes and that reduction of cyclic adenosine monophosphate (cAMP) production by inhibiting adenylyl cyclase in the spinal cord can alleviate diabetic neuropathy. METHODS: To this end, we examined the levels of cAMP, cAMP-dependent protein kinase (PKA) and cAMP response element-binding protein (CREB) in the spinal cord after the development of neuropathic pain in Zucker diabetic fatty (ZDF) rats with type 2 diabetes...
November 23, 2016: Canadian Journal of Diabetes
https://www.readbyqxmd.com/read/27888610/camp-independent-signal-pathways-stimulate-hyphal-morphogenesis-in-candida-albicans
#7
Salvatore M Parrino, Haoyu Si, Shamoon Naseem, Kevin Groudan, Justin Gardin, James B Konopka
The fungal pathogen Candida albicans can transition from budding to hyphal growth, which promotes biofilm formation and invasive growth into tissues. Stimulation of adenylyl cyclase to form cAMP induces hyphal morphogenesis. The failure of cells lacking adenylyl cyclase (cyr1Δ) to form hyphae has suggested that cAMP signaling is essential for hyphal growth. However, cyr1Δ mutants also grow slowly and have defects in morphogenesis, making it unclear whether hyphal inducers must stimulate cAMP, or if normal basal levels of cAMP are required to maintain cellular health needed for hyphal growth...
November 26, 2016: Molecular Microbiology
https://www.readbyqxmd.com/read/27888281/the-actions-of-relaxin-family-peptides-on-signal-transduction-pathways-activated-by-the-relaxin-family-peptide-receptor-rxfp4
#8
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...
November 26, 2016: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/27878759/loss-of-adenylyl-cyclase-type-5-in-the-dorsal-striatum-produces-autistic-like-behaviors
#9
Hannah Kim, Yunjin Lee, Jin-Young Park, Ji-Eun Kim, Tae-Kyung Kim, Juli Choi, Jung-Eun Lee, Eun-Hwa Lee, Daesoo Kim, Kyoung-Shim Kim, Pyung-Lim Han
Autism spectrum disorders (ASDs) are a heterogeneous group of psychiatric illness characterized by common core symptoms including sociability deficits and stereotyped behaviors. ASD is caused by various genetic and non-genetic factors. The genetic effects of autism-related genes are usually global and are presented with multiple symptoms, which hamper understanding of the mechanism through which the diverse causes of ASD produce common symptoms. In the present study, we demonstrate that genetic or molecular disruption of an array of molecular networks centered on adenylyl cyclase type-5 (AC5 or ADCY5) in the dorsal striatum produces autistic-like behaviors...
November 23, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27878579/g-protein-coupled-receptors-signaling-pathways-implicate-in-inflammatory-and-immune-response-of-rheumatoid-arthritis
#10
REVIEW
Jinling Shu, Feng Zhang, Lingling Zhang, Wei Wei
INTRODUCTION: G protein-coupled receptors (GPCRs) are transmembrane receptor proteins, which allow the transfer of signals across the membrane. Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovitis and accompanied with inflammatory and abnormal immune response. GPCRs signaling pathways play a significant role in inflammatory and immune response processes including RA. FINDINGS: In this review, we have focused on the advances in GPCRs signaling pathway implicating the inflammatory and immune response of RA...
November 23, 2016: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/27865066/newly-synthesized-camp-is-integrated-at-a-membrane-protein-complex-signalosome-to-ensure-receptor-response-specificity
#11
Raquel Guinzberg, Antonio Díaz-Cruz, Carlos Acosta-Trujillo, María Magdalena Vilchis-Landeros, Héctor Vázquez-Meza, Carlos Lozano-Flores, Natalia Chiquete-Felix, Alfredo Varela-Echavarría, Salvador Uribe-Carvajal, Héctor Riveros-Rosas, Enrique Piña
Spatiotemporal regulation of cAMP within the cell is required to achieve receptor-specific responses. The mechanism through which the cell selects a specific response to new synthesized cAMP is not fully understood. In hepatocyte plasma membranes, we identified two functional and independent cAMP-responsive signaling protein macrocomplexes that produce, use, degrade, and regulate their own non-diffusible (sequestered) cAMP pool to achieve their specific responses. Each complex responds to the stimulation of an adenosine G-protein coupled receptor (Ado-GPCR), bound to either A2A or A2B , but not simultaneously to both...
November 19, 2016: FEBS Journal
https://www.readbyqxmd.com/read/27864010/differentially-expressed-genes-in-the-testicular-tissues-of-adenylyl-cyclase-3-knockout-mice
#12
Jing Zhang, Yuan Yuan, Qingxiu Liu, Dong Yang, Mingshen Liu, Limin Shen, Yanfen Zhou, Zhenshan Wang
Adenylate cyclase 3 (AC3) is an important component of the cyclic adenosine 3',5'-monophosphate (cAMP) signaling pathway and converts adenosine triphosphate into cAMP. Male mice with AC3 deletion (AC3(-/-)) are sterile. However, the mechanical mechanism remains unclear. By TUNEL staining, we found that cell apoptosis in the testicular tissues of AC3(-/-) mice increased significantly compared with that in the wild-type (AC3(+/+)) mice. Differentially expressed genes regulated by AC3 in the testicular tissues were identified by gene chip hybridization...
November 15, 2016: Gene
https://www.readbyqxmd.com/read/27836216/regulation-of-ip3-receptors-by-cyclic-amp
#13
REVIEW
Colin W Taylor
Ca(2+) and cAMP are ubiquitous intracellular messengers and interactions between them are commonplace. Here the effects of cAMP on inositol 1,4,5-trisphosphate receptors (IP3Rs) are briefly reviewed. All three subtypes of IP3R are phosphorylated by cAMP-dependent protein kinase (PKA). This potentiates IP3-evoked Ca(2+) release through IP3R1 and IP3R2, but probably has little effect on IP3R3. In addition, cAMP can directly sensitize all three IP3R subtypes to IP3. The high concentrations of cAMP required for this PKA-independent modulation of IP3Rs is delivered to them within signalling junctions that include type 6 adenylyl cyclase and IP3R2...
November 6, 2016: Cell Calcium
https://www.readbyqxmd.com/read/27833594/candida-species-rewired-hyphae-developmental-programs-for-chlamydospore-formation
#14
Bettina Böttcher, Christine Pöllath, Peter Staib, Bernhard Hube, Sascha Brunke
Chlamydospore formation is a characteristic of many fungal species, among them the closely related human-pathogenic dimorphic yeasts Candida albicans and C. dubliniensis. Whereas function and regulation of filamentation are well-studied in these species, the basis of chlamydospore formation is mostly unknown. Here, we investigate the contribution of environmental and genetic factors and identified central proteins involved in species-specific regulation of chlamydosporulation. We show that specific nutrient levels strongly impact chlamydospore initiation, with starvation favoring sporulation and elevated levels of saccharides or peptone inhibiting it...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27830686/-beta-adrenoceptor-mediated-cyclic-amp-signal-in-different-types-of-cultured-nerve-cells-in-normoxic-and-hypoxic-conditions
#15
M Jóźwiak-Bębenista, A Wiktorowska-Owczarek, E Kowalczyk
β-adrenergic neurotransmission is an important factor regulating brain activity such as neuronal and glial survival, plasticity, membrane transport or cellular metabolism. Intracellular β-adrenergic signaling, via a stimulatory G protein (Gs), activates two major down-stream effectors, i.e., adenylyl cyclase (AC) and cAMP-dependent protein kinase A (PKA). The aim of this work was to study the ability of endogenous (adrenaline and noradrenaline) and exogenous (isoprenaline) β-adrenergic receptor agonists to increase cAMP in different types of nerve cells...
September 2016: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/27828947/a-cannabinoid-link-between-mitochondria-and-memory
#16
Etienne Hebert-Chatelain, Tifany Desprez, Román Serrat, Luigi Bellocchio, Edgar Soria-Gomez, Arnau Busquets-Garcia, Antonio Christian Pagano Zottola, Anna Delamarre, Astrid Cannich, Peggy Vincent, Marjorie Varilh, Laurie M Robin, Geoffrey Terral, M Dolores García-Fernández, Michelangelo Colavita, Wilfrid Mazier, Filippo Drago, Nagore Puente, Leire Reguero, Izaskun Elezgarai, Jean-William Dupuy, Daniela Cota, Maria-Luz Lopez-Rodriguez, Gabriel Barreda-Gómez, Federico Massa, Pedro Grandes, Giovanni Bénard, Giovanni Marsicano
Cellular activity in the brain depends on the high energetic support provided by mitochondria, the cell organelles which use energy sources to generate ATP. Acute cannabinoid intoxication induces amnesia in humans and animals, and the activation of type-1 cannabinoid receptors present at brain mitochondria membranes (mtCB1) can directly alter mitochondrial energetic activity. Although the pathological impact of chronic mitochondrial dysfunctions in the brain is well established, the involvement of acute modulation of mitochondrial activity in high brain functions, including learning and memory, is unknown...
November 9, 2016: Nature
https://www.readbyqxmd.com/read/27826057/adenylyl-cyclase-5-links-changes-in-calcium-homeostasis-to-camp-dependent-cyst-growth-in-polycystic-liver-disease
#17
Carlo Spirli, Valeria Mariotti, Ambra Villani, Luca Fabris, Romina Fiorotto, Mario Strazzabosco
BACKGROUND/AIMS: Genetic defects in Polycystins -1 or -2 (PC1 or PC2) cause polycystic liver disease associated with ADPKD (PLD-ADPKD). Progressive cyst growth is sustained by a cAMP-dependent Ras/ERK/HIFα pathway leading to increased autocrine/paracrine VEGF-A signalling. In PC2-defective cholangiocytes, store-operated Ca(2+) entry (SOCE), intracellular and endoplasmic reticulum [Ca(2+)]ER levels are reduced, while cAMP production in response to [Ca(2+)]ER depletion is increased. We hypothesized that in PC2-defective cells, in response to [Ca(2+)]ER depletion, the Ca(2+)-inhibitable adenylyl-cyclases AC5 or AC6 are activated by the ER chaperon STIM1 resulting in cAMP/PKA-dependent Ras/ERK/HIFα pathway activation...
November 5, 2016: Journal of Hepatology
https://www.readbyqxmd.com/read/27821621/dopamine-d1a-directly-interacts-with-otoferlin-synaptic-pathway-proteins-ca2-and-phosphorylation-underlie-an-nsf-to-ap2mu1-molecular-switch
#18
Dakshnamurthy Selvakumar, Marian J Drescher, Nathan A Deckard, Neeliyath A Ramakrishnan, Barbara J Morley, Dennis G Drescher
Dopamine receptors regulate exocytosis via protein-protein interactions (PPIs) as well as via adenylyl cyclase transduction pathways. Evidence has been obtained for PPIs in inner ear hair cells coupling D1A to SNARE-related proteins snapin, otoferlin, NSF, and AP2mu1, dependent on [Ca(2+)] and phosphorylation. Specifically, the carboxy terminus of dopamine D1A was found to directly bind t-SNARE-associated protein snapin in teleost and mammalian hair cell models by yeast two-hybrid and pull-down assays, and snapin directly interacts with  hair cell calcium-sensor otoferlin...
November 7, 2016: Biochemical Journal
https://www.readbyqxmd.com/read/27818454/vidarabine-an-anti-herpes-virus-agent-protects-against-the-development-of-heart-failure-with-relatively-mild-side-effects-on-cardiac-function-in-a-canine-model-of-pacing-induced-dilated-cardiomyopathy
#19
Takashi Nakamura, Takayuki Fujita, Megumi Kishimura, Kenji Suita, Yuko Hidaka, Wenqian Cai, Masanari Umemura, Utako Yokoyama, Masami Uechi, Yoshihiro Ishikawa
BACKGROUND: In heart failure patients, chronic hyperactivation of sympathetic signaling is known to exacerbate cardiac dysfunction. In this study, the cardioprotective effect of vidarabine, an anti-herpes virus agent, which we identified as a cardiac adenylyl cyclase inhibitor, in dogs with pacing-induced dilated cardiomyopathy (DCM) was evaluated. In addition, the adverse effects of vidarabine on basal cardiac function was compared to those of the β-blocker, carvedilol.Methods and Results:Vidarabine and carvedilol attenuated the development of pacing-induced systolic dysfunction significantly and with equal effectiveness...
November 5, 2016: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/27813476/ad%C3%A3-nylyl-cyclases-et-transdiff%C3%A3-renciation-des-cellules-musculaires-lisses-vasculaires-r%C3%A3-le-dans-le-remodelage-vasculaire-pathologique
#20
Marie Gueguen, Benjamin Vallin, Martine Glorian, Régis Blaise, Isabelle Limon
In response to various types of vascular stress, the smooth muscle cells of the vessel wall (VSMCs) change phenotype and acquire the capacity to react to abnormal signals. This phenomenon favors the involvement of these cells in the development of major vascular diseases, such as atherosclerosis, and some complications of angioplasty, such as restenosis. The cyclic adenosine monophosphate (cAMP) pathway plays a key role in the integration of stimuli from the immediate environment and in the development of cellular responses...
2016: Biologie Aujourd'hui
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