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Adenylyl cyclases

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https://www.readbyqxmd.com/read/28345252/amplification-of-fsh-signaling-by-cftr-and-nuclear-soluble-adenylyl-cyclase-in-the-ovary
#1
Hui Chen, Hsiao Chang Chan
cAMP/PKA pathway is one of the most important signaling pathways widely distributed in most eukaryotic cells. The activation of the canonical cAMP/PKA pathway depends on transmembrane adenylyl cyclase (tmAC). Recently, soluble adenylyl cyclase (sAC), which is activated by HCO3(-) or Ca(2+) , emerges to provide an alternative way to activate cAMP/PKA pathway with the cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated Cl(-) / HCO3(-) -conducting anion channel, as a key player. This review summarizes new progress in the investigation of the CFTR/HCO3(-) -dependent sAC signaling and its essential role in various reproductive processes, particularly in ovarian functions...
March 27, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28336405/photoactivation-mechanism-of-a-bacterial-light-regulated-adenylyl-cyclase
#2
Robert Lindner, Elisabeth Hartmann, Miroslaw Tarnawski, Andreas Winkler, Daniel Frey, Jochen Reinstein, Anton Meinhart, Ilme Schlichting
Light-regulated enzymes enable organisms to quickly respond to changing light conditions. We characterize a photoactivatable adenylyl cyclase from Beggiatoa sp. (bPAC) that translates a blue light signal into production of the second messenger cyclic AMP. bPAC contains a BLUF photoreceptor domain that senses blue light using a flavin chromophore, linked to an adenylyl cyclase (AC) domain. We present a dark state crystal structure of bPAC that closely resembles the recently published structure of the homologous OaPAC from Oscillatoria acuminata...
March 20, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28336329/an-aromatic-amino-acid-within-intracellular-loop-2-of-the-prostaglandin-ep2-receptor-is-a-prerequisite-for-selective-association-and-activation-of-g%C3%AE-s
#3
Akiko Yano, Yuko Takahashi, Hiromi Moriguchi, Tomoaki Inazumi, Tomoaki Koga, Akira Otaka, Yukihiko Sugimoto
We previously demonstrated that the aromatic moiety of Tyr(143) within the intracellular loop 2 (ICL2) region of the prostaglandin EP2 receptor plays a crucial role in Gs coupling. Here we investigated whether the ICL2 of the EP2 receptor directly binds to Gαs and whether an aromatic moiety affects this interaction. In Chinese hamster ovary cells, mutations of Tyr(143) reduced the ability of the EP2 receptor to interact with G proteins as demonstrated by GTPγS sensitivity, as well as the ability of agonist-induced cAMP formation, with the rank order of Phe>Tyr (wild-type)=Trp>Leu>Ala (=0)...
March 21, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28333280/hcg-activates-the-erk1-2-mitogen-activated-protein-kinase-pathway-in-human-endometrial-stromal-cells-transiently-increasing-the-progesterone-receptor-and-regulating-genes-associated-with-endometrial-receptivity
#4
Alejandro Tapia-Pizarro, Sebastián Archiles, Felipe Argandoña, Cecilia Valencia, Keyla Zavaleta, María Cecilia Johnson, Reinaldo González-Ramos, Luigi Devoto
STUDY QUESTION: How does hCG signal in human endometrial stromal cells (ESCs) and what is its role in regulating ESC function? SUMMARY ANSWER: CG signaling in ESCs activates the extracellular signal-regulated protein kinases 1 and 2 (Erk1/2) pathway through exchange protein activated by cAMP (Epac) and transiently increases progesterone receptor (PR) transcript and protein expression and its transcriptional function. WHAT IS KNOWN ALREADY: hCG is one of the earliest embryo-derived secreted signals in the endometrium, which abundantly expresses LH/hCG receptors...
March 14, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/28330503/caffeine-modulates-glucocorticoid-induced-expression-of-ctgf-in-lung-epithelial-cells-and-fibroblasts
#5
Markus Fehrholz, Kirsten Glaser, Christian P Speer, Silvia Seidenspinner, Barbara Ottensmeier, Steffen Kunzmann
BACKGROUND: Although caffeine and glucocorticoids are frequently used to treat chronic lung disease in preterm neonates, potential interactions are largely unknown. While anti-inflammatory effects of glucocorticoids are well defined, their impact on airway remodeling is less characterized. Caffeine has been ascribed to positive effects on airway inflammation as well as remodeling. Connective tissue growth factor (CTGF, CCN2) plays a key role in airway remodeling and has been implicated in the pathogenesis of chronic lung diseases such as bronchopulmonary dysplasia (BPD) in preterm infants...
March 23, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28327356/type-2-inositol-trisphosphate-receptor-gene-expression-in-hepatocytes-is-regulated-by-cyclic-amp
#6
Emma Kruglov, M Ananthanarayanan, Pedro Sousa, Jittima Weerachayaphorn, Mateus T Guerra, Michael H Nathanson
The type 2 inositol 1,4,5-trisphosphate receptor (IP3R2) is the principal intracellular Ca(2+) release channel in hepatocytes, and so is important for bile secretion and other functions. IP3R2 activity is regulated in part by post-translational modifications but little is known about transcriptional regulation of its expression. We found that both IP3R2 mRNA and protein levels in liver were increased during fasting. Treatment of hepatocytes with forskolin or 8-CPT-cAMP also increased IP3R2, and this was reduced by actinomycin D...
March 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28326667/the-v2-receptor-antagonist-tolvaptan-raises-cytosolic-calcium-and-prevents-aqp2-trafficking-and-function-an-in-vitro-and-in-vivo-assessment
#7
Grazia Tamma, Annarita Di Mise, Marianna Ranieri, Ari Geller, Roberto Tamma, Alberta Zallone, Giovanna Valenti
Tolvaptan, a selective vasopressin V2 receptor antagonist, is a new generation diuretic. Its clinical efficacy is in principle due to impaired vasopressin-regulated water reabsorption via aquaporin-2 (AQP2). Nevertheless, no direct in vitro evidence that tolvaptan prevents AQP2-mediated water transport, nor that this pathway is targeted in vivo in patients with syndrome of inappropriate antidiuresis (SIAD) has been provided. The effects of tolvaptan on the vasopressin-cAMP/PKA signalling cascade were investigated in MDCK cells expressing endogenous V2R and in mouse kidney...
March 21, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28322590/randomized-clinical-trials-of-gene-transfer-for-heart-failure-with-reduced-ejection-fraction
#8
William F Penny, H Kirk Hammond
Despite improvement in drug and device therapy for heart failure, hospitalization rates and mortality have changed little in the past decade. Randomized clinical trials using gene transfer to improve function of the failing heart are the focus of this review. Four randomized clinical trials of gene transfer in heart failure with reduced ejection fraction (HFrEF) have been published. Each enrolled patients with stable symptomatic HFrEF and used either intracoronary delivery of a virus vector or endocardial injection of a plasmid (1 trial)...
March 21, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28322171/dopaminergic-modulation-of-sleep-wake-states
#9
Andrea Herrera-Solís, Wendy Herrera-Morales, Luis Núñez-Jaramillo, Oscar Arias-Carrión
The role of dopamine in sleep-wake regulation is associated as a wakefulness-promoting agent. For the clinical treatment of excessive daytime sleepiness, drugs have been commonly used to increase dopamine release. However, sleep disorders or lack of sleep is related to several dopamine-related disorders. The effects of dopaminergic agents, nevertheless, are mediated by two families of dopamine receptors, D1 and D2-like receptors; the first family increases adenylyl cyclase activity and the second inhibits adenylyl cyclase...
March 20, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28302905/protein-kinase-a-regulates-the-ras-rap1-and-torc2-pathways-in-response-to-the-chemoattractant-camp-in-dictyostelium
#10
Margarethakay Scavello, Alexandra R Petlick, Ramya Ramesh, Valery F Thompson, Pouya Lotfi, Pascale G Charest
Efficient directed migration requires tight regulation of chemoattractant signal transduction pathways in both space and time, but the mechanisms involved in such regulation are not well understood. Here, we investigated the role of Protein Kinase A (PKA) in controlling signaling of the chemoattractant cAMP in Dictyostelium We found that cells lacking PKA display severe chemotaxis defects, including impaired directional sensing. Although PKA is an important regulator of developmental gene expression, including the cAMP receptor cAR1, our studies using exogenously expressed cAR1 in cells lacking PKA, cells lacking adenylyl cyclase A (ACA), and cells treated with the PKA-selective pharmacological inhibitor H89, suggest that PKA controls chemoattractant signal transduction, in part, through the regulation of RasG, Rap1, and TORC2...
March 16, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28302718/a-unique-choanoflagellate-enzyme-rhodopsin-with-cyclic-nucleotide-phosphodiesterase-activity
#11
Kazuho Yoshida, Satoshi P Tsunoda, Leonid S Brown, Hideki Kandori
Photoactivated adenylyl cyclase (PAC) and guanylyl cyclase rhodopsin (Rh-GC) increase the concentrations of intracellular cyclic nucleotides upon illumination, serving as promising second-generation tools in optogenetics. To broaden arsenal of such tools, it is desirable to have light-activatable enzymes which can decrease cyclic nucleotide concentrations in cells. Here, we report on an unusual microbial rhodopsin which may be able to meet the demand. It is found in the choanoflagellate Salpingoeca rosetta and contains a C-terminal cyclic nucleotide phosphodiesterase (PDE) domain...
March 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28288148/natriuretic-peptide-c-receptor-in-the-developing-sheep-lung-role-in-perinatal-transition
#12
Bobby Mathew, Christopher A D'Angelis, Satyan Lakshminrusimha, Peter A Nickerson, June J Sokolowski, Vasantha H S Kumar, Huamei Wang, Karen A Wynn, Bruce A Holm, Rita M Ryan
BACKGROUND: At birth, the release of surfactant from Alveolar Type II (ATII) cells is stimulated by increased activity of the beta-adrenergic/adenylyl cyclase/cAMP- signaling cascade. Atrial natriuretic peptide (ANP) stimulates surfactant secretion through Natriuretic peptide receptor A (NPR-A). ANP inhibits adenylyl cyclase activity through its binding to NPR-C. We wished to further understand the role of the NPR-C in perinatal transition. METHODS: We studied fetal and newborn sheep ATII expression of NPR-C and surfactant secretion in isolated ATIIs by measuring (3)[H] choline release into the media...
March 13, 2017: Pediatric Research
https://www.readbyqxmd.com/read/28261668/staurosporine-induces-filamentation-in-the-human-fungal-pathogen-candida-albicans-via-signaling-through-cyr1-and-protein-kinase-a
#13
Jinglin L Xie, Teresa R O'Meara, Elizabeth J Polvi, Nicole Robbins, Leah E Cowen
Protein kinases are key regulators of signal transduction pathways that participate in diverse cellular processes. In fungal pathogens, kinases regulate signaling pathways that govern drug resistance, stress adaptation, and pathogenesis. The impact of kinases on the fungal regulatory circuitry has recently garnered considerable attention in the opportunistic fungal pathogen Candida albicans, which is a leading cause of human morbidity and mortality. Complex regulatory circuitry governs the C. albicans morphogenetic transition between yeast and filamentous growth, which is a key virulence trait...
March 2017: MSphere
https://www.readbyqxmd.com/read/28255005/international-union-of-basic-and-clinical-pharmacology-ci-structures-and-small-molecule-modulators-of-mammalian-adenylyl-cyclases
#14
REVIEW
Carmen W Dessauer, Val J Watts, Rennolds S Ostrom, Marco Conti, Stefan Dove, Roland Seifert
Adenylyl cyclases (ACs) generate the second messenger cAMP from ATP. Mammalian cells express nine transmembrane AC (mAC) isoforms (AC1-9) and a soluble AC (sAC, also referred to as AC10). This review will largely focus on mACs. mACs are activated by the G-protein Gαs and regulated by multiple mechanisms. mACs are differentially expressed in tissues and regulate numerous and diverse cell functions. mACs localize in distinct membrane compartments and form signaling complexes. sAC is activated by bicarbonate with physiologic roles first described in testis...
April 2017: Pharmacological Reviews
https://www.readbyqxmd.com/read/28249274/the-emerging-role-of-soluble-adenylyl-cyclase-in-primary-biliary-cholangitis
#15
Jung-Chin Chang, Ulrich Beuers, Ronald P J Oude Elferink
BACKGROUND: Primary biliary cholangitis (PBC; previously referred to as primary biliary cirrhosis) is a chronic fibrosing cholangiopathy with the signature of an autoimmune disease and features of intrahepatic cholestasis. Immunosuppressing treatments are largely unsuccessful. Responsiveness to ursodeoxycholic acid and reduced expression of anion exchanger 2 (AE2) on canalicular membranes and small bile ducts underline the importance of bicarbonate transportation in its disease mechanism...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/28241436/gomisin-n-inhibits-melanogenesis-through-regulating-the-pi3k-akt-and-mapk-erk-signaling-pathways-in-melanocytes
#16
Jae Kyoung Chae, Lalita Subedi, Minsun Jeong, Yong Un Park, Chul Young Kim, Hakwon Kim, Sun Yeou Kim
Gomisin N, one of the lignan compounds found in Schisandra chinensis has been shown to possess anti-oxidative, anti-tumorigenic, and anti-inflammatory activities in various studies. Here we report, for the first time, the anti-melenogenic efficacy of Gomisin N in mammalian cells as well as in zebrafish embryos. Gomisin N significantly reduced the melanin content without cellular toxicity. Although it was not capable of modulating the catalytic activity of mushroom tyrosinase in vitro, Gomisin N downregulated the expression levels of key proteins that function in melanogenesis...
February 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28228402/aliskiren-increases-aquaporin-2-expression-and-attenuates-lithium-induced-nephrogenic-diabetes-insipidus
#17
Yu Lin, Tiezheng Zhang, Pinning Feng, Miaojuan Qiu, Qiaojuan Liu, Suchun Li, Peili Zheng, Yonglun Kong, Moshe Levi, Chunling Li, Weidong Wang
The direct renin inhibitor aliskiren has been shown to retain and persist in medullary collecting ducts even after treatment was discontinued, suggesting a new mechanism of action for this drug. The purpose of the present study was to investigate whether aliskiren regulates renal aquaporin expression in the collecting ducts and improves urinary concentrating defect induced by lithium in mice. The mice were either fed with normal chow or LiCl diet (40mM/kg dry food/day for 4 days and 20mM/kg dry food/day for last 3 days) for seven days...
February 22, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28223412/identification-of-a-selective-small-molecule-inhibitor-of-type-1-adenylyl-cyclase-activity-with-analgesic-properties
#18
Tarsis F Brust, Doungkamol Alongkronrusmee, Monica Soto-Velasquez, Tanya A Baldwin, Zhishi Ye, Mingji Dai, Carmen W Dessauer, Richard M van Rijn, Val J Watts
Adenylyl cyclase 1 (AC1) belongs to a group of adenylyl cyclases (ACs) that are stimulated by calcium in a calmodulin-dependent manner. Studies with AC1 knockout mice suggest that inhibitors of AC1 may be useful for treating pain and opioid dependence. However, nonselective inhibition of AC isoforms could result in substantial adverse effects. We used chemical library screening to identify a selective AC1 inhibitor with a chromone core structure that may represent a new analgesic agent. After demonstrating that the compound (ST034307) inhibited Ca(2+)-stimulated adenosine 3',5'-monophosphate (cAMP) accumulation in human embryonic kidney (HEK) cells stably transfected with AC1 (HEK-AC1 cells), we confirmed selectivity for AC1 by testing against all isoforms of membrane-bound ACs...
February 21, 2017: Science Signaling
https://www.readbyqxmd.com/read/28218269/enhanced-expression-of-adcy1-underlies-aberrant-neuronal-signalling-and-behaviour-in-a-syndromic-autism-model
#19
Ferzin Sethna, Wei Feng, Qi Ding, Alfred J Robison, Yue Feng, Hongbing Wang
Fragile X syndrome (FXS), caused by the loss of functional FMRP, is a leading cause of autism. Neurons lacking FMRP show aberrant mRNA translation and intracellular signalling. Here, we identify that, in Fmr1 knockout neurons, type 1 adenylyl cyclase (Adcy1) mRNA translation is enhanced, leading to excessive production of ADCY1 protein and insensitivity to neuronal stimulation. Genetic reduction of Adcy1 normalizes the aberrant ERK1/2- and PI3K-mediated signalling, attenuates excessive protein synthesis and corrects dendritic spine abnormality in Fmr1 knockout mice...
February 20, 2017: Nature Communications
https://www.readbyqxmd.com/read/28217833/lengthening-primary-cilia-enhances-cellular-mechanosensitivity
#20
M Spasic, C R Jacobs
The primary cilium is a mechanosensor in a variety of mammalian cell types, initiating and directing intracellular signalling cascades in response to external stimuli. When primary cilia formation is disrupted, cells have diminished mechanosensitivity and an abrogated response to mechanical stimulation. Due to this important role, we hypothesised that increasing primary cilia length would enhance the downstream response and therefore, mechanosensitivity. To test this hypothesis, we increased osteocyte primary cilia length with fenoldopam and lithium and found that cells with longer primary cilia were more mechanosensitive...
February 20, 2017: European Cells & Materials
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