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https://www.readbyqxmd.com/read/28327356/type-2-inositol-trisphosphate-receptor-gene-expression-in-hepatocytes-is-regulated-by-cyclic-amp
#1
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
#2
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/28323049/sutherlandia-frutescens-modulates-adrenal-hormone-biosynthesis-displays-anti-mineralocorticoid-and-serga-properties-acting-as-a-dissociated-glucocorticoid
#3
C A Sergeant, D Africander, P Swart, A C Swart
ETHNOPHARMACOLOGICAL RELEVANCE: Sutherlandia frutescens is a traditional African medicinal plant used in the treatment of stress and anxiety, while also exhibiting anti-inflammatory properties. AIM OF STUDY: The study aimed at linking anti-stress and anti-inflammatory properties of S. frutescens to its influence on glucocorticoid biosynthesis and the inflammatory response via steroid receptor interaction. MATERIALS AND METHODS: The influence of S...
March 18, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28321434/transient-creb-mediated-transcription-is-key-in-direct-neuronal-reprogramming
#4
Sergio Gascón, Felipe Ortega, Magdalena Götz
Combinations of neuronal determinants and/or small-molecules such as Forskolin (Fk) can be used to convert different cell types into neurons. As Fk is known to activate cAMP-dependent pathways including CREB-activity, we aimed here to determine the role of CREB in reprogramming - including its temporal profile. We show that transient expression of the dominant-positive CREB-VP16 followed by its inactivation mediated by the dominant-negative ICER improves neuronal conversion of astrocytes mediated by the neurogenic determinant Ascl1...
2017: Neurogenesis (Austin, Tex.)
https://www.readbyqxmd.com/read/28320871/essential-roles-of-l-type-amino-acid-transporter-1-in-syncytiotrophoblast-development-by-presenting-fusogenic-4f2hc
#5
Ryuichi Ohgaki, Takahiro Ohmori, Saori Hara, Saya Nakagomi, Masami Kanai-Azuma, Kazuko Kaneda-Nakashima, Suguru Okuda, Shushi Nagamori, Yoshikatsu Kanai
Layer(s) of epithelial syncytium, syncytiotrophoblast, differentiates from chorionic trophoblasts via cell fusion and separates maternal and fetal circulations in hemochorial placentas. L-type amino acid transporter 1 (LAT1) and its covalently-linked ancillary subunit 4F2hc are colocalized on both maternal and fetal surface of syncytiotrophoblasts, implying their roles in amino acid transfer through the placental barrier. In this study, LAT1 knockout, in addition, revealed a novel role of LAT1 in syncytiotrophoblast development...
March 20, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28306357/asthma-causes-inflammation-of-human-pulmonary-arteries-and-decreases-vasodilatation-induced-by-prostaglandin-i2-analogs
#6
Nabil Foudi, Aouatef Badi, Mounira Amrane, Wassim Hodroj
OBJECTIVE: Asthma is a chronic inflammatory disease associated with increased cardiovascular events. This study assesses the presence of inflammation and the vascular reactivity of pulmonary arteries in patients with acute asthma. METHODS: Rings of human pulmonary arteries obtained from non-asthmatic and asthmatic patients were set up in organ bath for vascular tone monitoring. Reactivity was induced by vasoconstrictor and vasodilator agents. Protein expression of inflammatory markers was detected by western blot...
February 21, 2017: Journal of Asthma: Official Journal of the Association for the Care of Asthma
https://www.readbyqxmd.com/read/28293165/-pyr-1-apelin-13-1-12-is-a-biologically-active-ace2-metabolite-of-the-endogenous-cardiovascular-peptide-pyr-1-apelin-13
#7
Peiran Yang, Rhoda E Kuc, Aimée L Brame, Alex Dyson, Mervyn Singer, Robert C Glen, Joseph Cheriyan, Ian B Wilkinson, Anthony P Davenport, Janet J Maguire
Aims: Apelin is a predicted substrate for ACE2, a novel therapeutic target. Our aim was to demonstrate the endogenous presence of the putative ACE2 product [Pyr(1)]apelin-13(1-12) in human cardiovascular tissues and to confirm it retains significant biological activity for the apelin receptor in vitro and in vivo. The minimum active apelin fragment was also investigated. Methods and Results: [Pyr(1)]apelin-13 incubated with recombinant human ACE2 resulted in de novo generation of [Pyr(1)]apelin-13(1-12) identified by mass spectrometry...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28290983/total-biosynthesis-of-the-cyclic-amp-booster-forskolin-from-coleus-forskohlii
#8
Irini Pateraki, Johan Andersen-Ranberg, Niels Bjerg Jensen, Sileshi Gizachew Wubshet, Allison Maree Heskes, Victor Forman, Björn Hallström, Britta Hamberger, Mohammed Saddik Motawia, Carl Erik Olsen, Dan Staerk, Jørgen Hansen, Birger Lindberg Møller, Bjoern Hamberger
Forskolin is a unique structurally complex labdane type diterpenoid used in the treatment of glaucoma and heart failure based on its activity as a cyclic AMP booster. Commercial production of forskolin relies exclusively on extraction from its only known natural source, the plant Coleus forskohlii, in which forskolin accumulates in the root cork. Here we report the discovery of five cytochrome P450s and two acetyltransferases which catalyze a cascade of reactions converting the forskolin precursor 13R-manoyl oxide into forskolin and a diverse array of additional labdane-type diterpenoids...
March 14, 2017: ELife
https://www.readbyqxmd.com/read/28287550/forskolin-induced-swelling-in-intestinal-organoids-an-in-vitro-assay-for-assessing-drug-response-in-cystic-fibrosis-patients
#9
Sylvia F Boj, Annelotte M Vonk, Marvin Statia, Jinyi Su, Robert R G Vries, Jeffrey M Beekman, Hans Clevers
Recently-developed cystic fibrosis transmembrane conductance regulator (CFTR)-modulating drugs correct surface expression and/or function of the mutant CFTR channel in subjects with cystic fibrosis (CF). Identification of subjects that may benefit from these drugs is challenging because of the extensive heterogeneity of CFTR mutations, as well as other unknown factors that contribute to individual drug efficacy. Here, we describe a simple and relatively rapid assay for measuring individual CFTR function and response to CFTR modulators in vitro...
February 11, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28286110/fast-transdifferentiation-of-human-wharton-s-jelly-mesenchymal-stem-cells-into-neurospheres-and-nerve-like-cells
#10
A R Bonilla-Porras, C Velez-Pardo, M Jimenez-Del-Rio
BACKGROUND: The human mesenchymal stem cells derived from Wharton's jelly tissue (hWJ-MSCs) represent a tool for cell-based therapies and regenerative medicine. hWJ-MSCs form neurospheres (NSs) within 3-7 days. No data is available to establish the neuro-phenotypic markers and time of formation of nerve-like (NLCs) and glial cells from NSs derived from hWJ-MSCs. NEW METHOD: hWJ-MSCs were incubated with Fast-N-Spheres medium for 24 and 72h. The new formed NSs were in turn incubated with forskolin in neurogenic NeuroForsk medium for 1-7days...
March 8, 2017: Journal of Neuroscience Methods
https://www.readbyqxmd.com/read/28276525/regulation-of-molecular-clock-oscillations-and-phagocytic-activity-via-muscarinic-ca-2-signaling-in-human-retinal-pigment-epithelial-cells
#11
Rina Ikarashi, Honami Akechi, Yuzuki Kanda, Alsawaf Ahmad, Kouhei Takeuchi, Eri Morioka, Takashi Sugiyama, Takashi Ebisawa, Masaaki Ikeda, Masayuki Ikeda
Vertebrate eyes are known to contain circadian clocks, however, the intracellular mechanisms regulating the retinal clockwork remain largely unknown. To address this, we generated a cell line (hRPE-YC) from human retinal pigmental epithelium, which stably co-expressed reporters for molecular clock oscillations (Bmal1-luciferase) and intracellular Ca(2+) concentrations (YC3.6). The hRPE-YC cells demonstrated circadian rhythms in Bmal1 transcription. Also, these cells represented circadian rhythms in Ca(2+)-spiking frequencies, which were canceled by dominant-negative Bmal1 transfections...
March 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28273890/cftr-is-involved-in-the-regulation-of-glucagon-secretion-in-human-and-rodent-alpha-cells
#12
Anna Edlund, Morten Gram Pedersen, Andreas Lindqvist, Nils Wierup, Malin Flodström-Tullberg, Lena Eliasson
Glucagon is the main counterregulatory hormone in the body. Still, the mechanism involved in the regulation of glucagon secretion from pancreatic alpha cells remains elusive. Dysregulated glucagon secretion is common in patients with Cystic Fibrosis (CF) that develop CF related diabetes (CFRD). CF is caused by a mutation in the Cl(-) channel Cystic fibrosis transmembrane conductance regulator (CFTR), but whether CFTR is present in human alpha cells and regulate glucagon secretion has not been investigated in detail...
December 2017: Scientific Reports
https://www.readbyqxmd.com/read/28257236/human-rhinovirus-infection-of-epithelial-cells-modulates-airway-smooth-muscle-migration
#13
Sami Shariff, Christopher Shelfoon, Neil S Holden, Suzanne L Traves, Shahina Wiehler, Cora Kooi, David Proud, Richard Leigh
RATIONALE: Airway remodeling, a characteristic feature of asthma, begins in early life. Recurrent human rhinovirus (HRV) infections are a potential inciting stimulus for remodeling. One component of airway remodeling is an increase in airway smooth muscle cell mass with a greater proximity of the airway smooth muscle cells (ASMC) to the airway epithelium. We asked whether human bronchial epithelial cells infected with HRV produced mediators that are chemotactic for ASMC. METHODS: ASMC migration was investigated using the modified Boyden Chamber and the xCELLigence Real-Time Cell Analyzer...
March 3, 2017: American Journal of Respiratory Cell and Molecular Biology
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/28245668/first-human-experience-with-autologous-schwann-cells-to-supplement-sciatic-nerve-repair-report-of-2-cases-with-long-term-follow-up
#15
Zachary C Gersey, S Shelby Burks, Kim D Anderson, Marine Dididze, Aisha Khan, W Dalton Dietrich, Allan D Levi
OBJECTIVE Long-segment injuries to large peripheral nerves present a challenge to surgeons because insufficient donor tissue limits repair. Multiple supplemental approaches have been investigated, including the use of Schwann cells (SCs). The authors present the first 2 cases using autologous SCs to supplement a peripheral nerve graft repair in humans with long-term follow-up data. METHODS Two patients were enrolled in an FDA-approved trial to assess the safety of using expanded populations of autologous SCs to supplement the repair of long-segment injuries to the sciatic nerve...
March 2017: Neurosurgical Focus
https://www.readbyqxmd.com/read/28242307/molecular-identification-of-the-dyn-kor-system-and-its-potential-role-in-the-reproductive-axis-of-goldfish
#16
Yali Liu, Shuisheng Li, Qing Wang, Yu Chen, Xin Qi, Yun Liu, Xiaochun Liu, Haoran Lin, Yong Zhang
To ascertain the significance of the dynorphin/kappa-opioid receptor (Dyn/Kor) system in fish reproduction, prodynorphin (pdyn) cDNA was cloned from goldfish. Two Dyn peptides (DynA and DynB) are present in the goldfish prodynorphin precursor. Both DynA and DynB are biologically active as they are able to functionally interact with the goldfish Kor expressed in cultured eukaryotic cells to suppress forskolin-induced CRE promoter activity. RT-PCR analysis showed that pdyn is widely expressed in brain regions, with the highest expression in hypothalamus...
February 24, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28235949/bmp4-inhibits-pdgf-induced-proliferation-and-collagen-synthesis-via-pka-mediated-inhibition-of-calpain-2-in-pulmonary-artery-smooth-muscle-cells
#17
PengCheng Cai, Laszlo Kovacs, Sam Dong, Guangyu Wu, Yunchao Su
In the present study, we investigated the effect of bone morphogenetic protein 4 (BMP4) on PDGF-induced proliferation and collagen synthesis in PASMCs. Normal human PASMCs were incubated with and without PDGF-BB in the absence and presence of BMP4 for 0.5 to 24 h. Then the protein levels of collagen-I, p-Smad2/3, p-Smad1/5, and intracellular active TGFβ1, calpain activity and cell proliferation were measured. The results showed that BMP4 induced an increase in p-Smad1/5 but had no effect on the protein levels of collagen-I, p-Smad2/3, and intracellular active TGFβ1, and calpain activity in PASMCs...
February 24, 2017: American Journal of Physiology. Lung Cellular and Molecular 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/28222855/direct-growth-inhibitory-effects-of-prostaglandin-e2-in%C3%A2-pancreatic-cancer-cells-in%C3%A2-vitro-through-an-ep4-pka-mediated-mechanism
#19
Andrea Schmidt, James Sinnett-Smith, Steven Young, Hui-Hua Chang, O Joe Hines, David W Dawson, Enrique Rozengurt, Guido Eibl
BACKGROUND: There is strong evidence linking inflammation and the development of pancreatic ductal adenocarcinoma. Cyclooxygenase-2 (COX-2) and COX-2-derived PGE2 are overexpressed in human and murine pancreatic ductal adenocarcinoma. Several studies have demonstrated an important role of COX-2-derived PGE2 in tumor-stroma interactions; however, the direct growth effects of prostaglandin E2 (PGE2) on pancreatic ductal adenocarcinoma cells is less well defined. Our aim was to investigate the effects of PGE2 on pancreatic ductal adenocarcinoma cell growth and to characterize the underlying mechanisms...
February 17, 2017: Surgery
https://www.readbyqxmd.com/read/28216156/exchange-proteins-directly-activated-by-camp-induce-the-proliferation-of-rat-anterior-pituitary-gh3-cells-via-the-activation-of-extracellular-signal-regulated-kinase
#20
Wei Sun, Wei Jiao, Yimin Huang, Ran Li, Zhuo Zhang, Junwen Wang, Ting Lei
Cyclic adenosine 3'-5'-monophosphate (cAMP) plays a crucial role in regulating pituitary cell proliferation and hormone synthesis. Recent evidence suggests that exchange proteins directly activated by cAMP (Epacs) may mediate the effects of cAMP. Here we used rat anterior pituitary GH3 cells as the experiment model to demonstrate that forskolin increased the proliferation of GH3 cells and the phosphorylation of ERK1/2, and these effects were inhibited by PKA or Epac inhibitors. Epac activator 8-pCPT-2'-O-Me-cAMP increased GH3 cell proliferation and this was blocked by ESI-09, an Epac inhibitor...
April 1, 2017: Biochemical and Biophysical Research Communications
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