scholarly journals Okamoto model for necrosis and its expansions, CD38-cyclic ADP-ribose signal system for intracellular Ca2+ mobilization and Reg (Regenerating gene protein)-Reg receptor system for cell regeneration

2021 ◽  
Vol 97 (8) ◽  
pp. 423-461
Author(s):  
Hiroshi OKAMOTO ◽  
Shin TAKASAWA
Keyword(s):  
Cell Regeneration ◽  
Signal System ◽  
Receptor System ◽  
Cyclic Adp Ribose ◽  
Intracellular Ca

Role of cyclic ADP-ribose in the regulation of [Ca2+]i in porcine tracheal smooth muscle

1998 ◽  
Vol 274 (6) ◽  
pp. C1653-C1660 ◽  
Author(s):  
Y. S. Prakash ◽  
Mathur S. Kannan ◽  
Timothy F. Walseth ◽  
Gary C. Sieck
Keyword(s):  
Smooth Muscle ◽  
Second Messenger ◽  
Ruthenium Red ◽  
Tracheal Smooth Muscle ◽  
Cyclic Adp Ribose ◽  
Intracellular Ca ◽  
Subsequent Exposure ◽  
Trisphosphate Receptor ◽  
Dose Dependent Increase

The purpose of the present study was to determine whether cyclic ADP-ribose (cADPR) acts as a second messenger for Ca2+ release through ryanodine receptor (RyR) channels in tracheal smooth muscle (TSM). Freshly dissociated porcine TSM cells were permeabilized with β-escin, and real-time confocal microscopy was used to examine changes in intracellular Ca2+ concentration ([Ca2+]i). cADPR (10 nM–10 μM) induced a dose-dependent increase in [Ca2+]i, which was blocked by the cADPR receptor antagonist 8-amino-cADPR (20 μM) and by the RyR blockers ruthenium red (10 μM) and ryanodine (10 μM), but not by the inositol 1,4,5-trisphosphate receptor blocker heparin (0.5 mg/ml). During steady-state [Ca2+]ioscillations induced by acetylcholine (ACh), addition of 100 nM and 1 μM cADPR increased oscillation frequency and decreased peak-to-trough amplitude. ACh-induced [Ca2+]ioscillations were blocked by 8-amino-cADPR; however, 8-amino-cADPR did not block the [Ca2+]iresponse to a subsequent exposure to caffeine. These results indicate that cADPR acts as a second messenger for Ca2+ release through RyR channels in TSM cells and may be necessary for initiating ACh-induced [Ca2+]ioscillations.

scholarly journals Synthesis of cyclic N 1-pentylinosine phosphate, a new structurally reduced cADPR analogue with calcium-mobilizing activity on PC12 cells

2015 ◽  
Vol 11 ◽  
pp. 2689-2695 ◽  
Author(s):  
Ahmed Mahal ◽  
Stefano D’Errico ◽  
Nicola Borbone ◽  
Brunella Pinto ◽  
Agnese Secondo ◽  
...  
Keyword(s):  
Pc12 Cells ◽  
Neuronal Cells ◽  
Phosphate Group ◽  
Phosphodiester Bond ◽  
Cyclic Adp Ribose ◽  
Intracellular Ca ◽  
Biological Tests

Cyclic N 1-pentylinosine monophosphate (cpIMP), a novel simplified inosine derivative of cyclic ADP-ribose (cADPR) in which the N 1-pentyl chain and the monophosphate group replace the northern ribose and the pyrophosphate moieties, respectively, was synthesized. The role played by the position of the phosphate group in the key cyclization step, which consists in the formation of a phosphodiester bond, was thoroughly investigated. We have also examined the influence of the phosphate bridge on the ability of cpIMP to mobilize Ca2+ in PC12 neuronal cells in comparison with the pyrophosphate bridge present in the cyclic N 1-pentylinosine diphosphate analogue (cpIDP) previously synthesized in our laboratories. The preliminary biological tests indicated that cpIMP and cpIDP induce a rapid increase of intracellular Ca2+ concentration in PC12 neuronal cells.

Imaging of intracellular calcium stores in single permeabilized lens cells

1999 ◽  
Vol 276 (2) ◽  
pp. C426-C434 ◽  
Author(s):  
Grant C. Churchill ◽  
Charles F. Louis
Keyword(s):  
Intracellular Calcium ◽  
Calcium Stores ◽  
Fura 2 ◽  
Intracellular Calcium Stores ◽  
Cyclic Adp Ribose ◽  
Inositol 1,4,5 Trisphosphate ◽  
Lens Cells ◽  
Intracellular Ca

Intracellular Ca2+ stores in permeabilized sheep lens cells were imaged with mag-fura 2 to characterize their distribution and sensitivity to Ca2+-releasing agents. Inositol 1,4,5-trisphosphate (IP3) or cyclic ADP-ribose (cADPR) released Ca2+ from intracellular Ca2+ stores that were maintained by an ATP-dependent Ca2+ pump. The IP3 antagonist heparin inhibited IP3- but not cADPR-mediated Ca2+ release, whereas the cADPR antagonist 8-amino-cADPR inhibited cADPR- but not IP3-mediated Ca2+ release, indicating that IP3 and cADPR were operating through separate mechanisms. A Ca2+ store sensitive to IP3, cADPR, and thapsigargin appeared to be distributed throughout all intracellular regions. In some cells a Ca2+ store insensitive to IP3, cADPR, thapsigargin, and 2,4-dinitrophenol, but not ionomycin, was present in a juxtanuclear region. We conclude that lens cells contain intracellular Ca2+ stores that are sensitive to IP3, cADPR, and thapsigargin, as well as a Ca2+store that appears insensitive to all these agents.

Regulation of store-operated Ca2+ entry by CD38 in human airway smooth muscle

2008 ◽  
Vol 294 (2) ◽  
pp. L378-L385 ◽  
Author(s):  
Gary C. Sieck ◽  
Thomas A. White ◽  
Michael A. Thompson ◽  
Christina M. Pabelick ◽  
Mark E. Wylam ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Critical Role ◽  
Human Airway Smooth Muscle ◽  
Cd38 Expression ◽  
Adp Ribosyl Cyclase ◽  
Cyclic Adp Ribose ◽  
Intracellular Ca ◽  
Interfering Rna ◽  
Synthesis And Degradation

The ectoenzyme CD38 catalyzes synthesis and degradation of cyclic ADP ribose in airway smooth muscle (ASM). The proinflammatory cytokine TNFα, which enhances agonist-induced intracellular Ca2+ ([Ca2+]i) responses, has been previously shown to increases CD38 expression. In the present study, we tested the hypothesis that the effects of TNFα on CD38 expression vs. changes in [Ca2+]i regulation in ASM cells are linked. Using isolated human ASM cells, CD38 expression was either increased (transfection) or knocked down [small interfering RNA (siRNA)], and [Ca2+]i responses to sarcoplasmic reticulum depletion [i.e., store-operated Ca2+ entry (SOCE)] were evaluated in the presence vs. absence of TNFα. Results confirmed that TNFα significantly increased CD38 expression and ADP-ribosyl cyclase activity, an effect inhibited by CD38 siRNA, but unaltered by CD38 overexpression. CD38 suppression blunted, whereas overexpression enhanced, ACh-induced [Ca2+]i responses. TNFα-induced enhancement of [Ca2+]i response to agonist was blunted by CD38 suppression, but enhanced by CD38 overexpression. Finally, TNFα-induced increase in SOCE was blunted by CD38 siRNA and potentiated by CD38 overexpression. Overall, these results indicate a critical role for CD38 in TNFα-induced enhancement of [Ca2+]i in human ASM cells, and potentially to TNFα augmentation of airway responsiveness.

scholarly journals The Oxytocin-Oxytocin Receptor System and Its Antagonists as Tocolytic Agents

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Nikolaos Vrachnis ◽  
Fotodotis M. Malamas ◽  
Stavros Sifakis ◽  
Efthymios Deligeoroglou ◽  
Zoe Iliodromiti
Keyword(s):  
Preterm Labor ◽  
Oxytocin Receptor ◽  
Uterine Contractility ◽  
Receptor Antagonists ◽  
Receptor System ◽  
Main Pathway ◽  
Intracellular Ca ◽  
Oxytocin Antagonists ◽  
Tocolytic Agents ◽  
G Protein Coupled

Oxytocin, a hormone involved in numerous physiologic processes, plays a central role in the mechanisms of parturition and lactation. It acts through its receptor, which belongs to the G-protein-coupled receptor superfamily, while Gq/phospholipase C (PLC)/inositol 1,4,5-triphosphate (InsP3) is the main pathway via which it exerts its action in the myometrium. Changes in receptor levels, receptor desensitization, and locally produced oxytocin are factors that influence the effect of oxytocin on uterine contractility in labor. Activation of oxytocin receptor causes myometrial contractions by increasing intracellular Ca+2and production of prostaglandins. Since oxytocin induces contractions, the inhibition of its action has been a target in the management of preterm labor. Atosiban is today the only oxytocin receptor antagonist that is available as a tocolytic. However, the quest for oxytocin receptor antagonists with a better pharmacological profile has led to the synthesis of peptide and nonpeptide molecules such as barusiban, retosiban, L-368,899, and SSR-126768A. Many of these oxytocin receptor antagonists are used only as pharmacological tools, while others have tocolytic action. In this paper, we summarize the action of oxytocin and its receptor and we present an overview of the clinical and experimental data of oxytocin antagonists and their tocolytic action.

scholarly journals Cluster of Differentiation 38 (CD38) Mediates Bile Acid-induced Acinar Cell Injury and Pancreatitis through Cyclic ADP-ribose and Intracellular Calcium Release

2013 ◽  
Vol 288 (38) ◽  
pp. 27128-27137 ◽  
Author(s):  
Abrahim I. Orabi ◽  
Kamaldeen A. Muili ◽  
Tanveer A. Javed ◽  
Shunqian Jin ◽  
Thottala Jayaraman ◽  
...  
Keyword(s):  
Bile Acid ◽  
Ryanodine Receptor ◽  
Acinar Cell ◽  
Calcium Release ◽  
Cell Injury ◽  
Acinar Cells ◽  
Pancreatic Acinar Cells ◽  
Iodide Uptake ◽  
Cyclic Adp Ribose ◽  
Intracellular Ca

Aberrant Ca2+ signals within pancreatic acinar cells are an early and critical feature in acute pancreatitis, yet it is unclear how these signals are generated. An important mediator of the aberrant Ca2+ signals due to bile acid exposure is the intracellular Ca2+ channel ryanodine receptor. One putative activator of the ryanodine receptor is the nucleotide second messenger cyclic ADP-ribose (cADPR), which is generated by an ectoenzyme ADP-ribosyl cyclase, CD38. In this study, we examined the role of CD38 and cADPR in acinar cell Ca2+ signals and acinar injury due to bile acids using pharmacologic inhibitors of CD38 and cADPR as well as mice deficient in Cd38 (Cd38−/−). Cytosolic Ca2+ signals were imaged using live time-lapse confocal microscopy in freshly isolated mouse acinar cells during perifusion with the bile acid taurolithocholic acid 3-sulfate (TLCS; 500 μm). To focus on intracellular Ca2+ release and to specifically exclude Ca2+ influx, cells were perifused in Ca2+-free medium. Cell injury was assessed by lactate dehydrogenase leakage and propidium iodide uptake. Pretreatment with either nicotinamide (20 mm) or the cADPR antagonist 8-Br-cADPR (30 μm) abrogated TLCS-induced Ca2+ signals and cell injury. TLCS-induced Ca2+ release and cell injury were reduced by 30 and 95%, respectively, in Cd38-deficient acinar cells compared with wild-type cells (p < 0.05). Cd38-deficient mice were protected against a model of bile acid infusion pancreatitis. In summary, these data indicate that CD38-cADPR mediates bile acid-induced pancreatitis and acinar cell injury through aberrant intracellular Ca2+ signaling.

Cyclic ADP ribose-mediated Ca2+ signaling in mediating endothelial nitric oxide production in bovine coronary arteries

2006 ◽  
Vol 290 (3) ◽  
pp. H1172-H1181 ◽  
Author(s):  
Guo Zhang ◽  
Eric G. Teggatz ◽  
Andrew Y. Zhang ◽  
Matthew J. Koeberl ◽  
Fan Yi ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Coronary Arteries ◽  
Ryanodine Receptors ◽  
No Production ◽  
Signaling Mechanism ◽  
Adp Ribosyl Cyclase ◽  
Cyclic Adp Ribose ◽  
Intracellular Ca ◽  
A Cell ◽  
Endothelial Nitric Oxide

The present study tested the hypothesis that cyclic ADP ribose (cADPR) serves as a novel second messenger to mediate intracellular Ca2+ mobilization in coronary arterial endothelial cells (CAECs) and thereby contributes to endothelium-dependent vasodilation. In isolated and perfused small bovine coronary arteries, bradykinin (BK)-induced concentration-dependent vasodilation was significantly attenuated by 8-bromo-cADPR (a cell-permeable cADPR antagonist), ryanodine (an antagonist of ryanodine receptors), or nicotinamide (an ADP-ribosyl cyclase inhibitor). By in situ simultaneously fluorescent monitoring, Ca2+ transient and nitric oxide (NO) levels in the intact coronary arterial endothelium preparation, 8-bromo-cADPR (30 μM), ryanodine (50 μM), and nicotinamide (6 mM) substantially attenuated BK (1 μM)-induced increase in intracellular [Ca2+] by 78%, 80%, and 74%, respectively, whereas these compounds significantly blocked BK-induced NO increase by about 80%, and inositol 1,4,5-trisphosphate receptor blockade with 2-aminethoxydiphenyl borate (50 μM) only blunted BK-induced Ca2+-NO signaling by about 30%. With the use of cADPR-cycling assay, it was found that inhibition of ADP-ribosyl cyclase by nicotinamide substantially blocked BK-induced intracellular cADPR production. Furthermore, HPLC analysis showed that the conversion rate of β-nicotinamide guanine dinucleotide into cyclic GDP ribose dramatically increased by stimulation with BK, which was blockable by nicotinamide. However, U-73122, a phospholipase C inhibitor, had no effect on this BK-induced increase in ADP-ribosyl cyclase activity for cADPR production. In conclusion, these results suggest that cADPR importantly contributes to BK- and A-23187-induced NO production and vasodilator response in coronary arteries through its Ca2+ signaling mechanism in CAECs.

scholarly journals Regulation of Angiogenic Functions by Angiopoietins through Calcium-Dependent Signaling Pathways

2015 ◽  
Vol 2015 ◽  
pp. 1-14 ◽  
Author(s):  
Irene Pafumi ◽  
Annarita Favia ◽  
Guido Gambara ◽  
Francesca Papacci ◽  
Elio Ziparo ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
The Other ◽  
Complex Interplay ◽  
Receptor System ◽  
Scratch Assay ◽  
Calcium Dependent ◽  
Intracellular Calcium Mobilization ◽  
Intracellular Ca ◽  
Angiopoietin 1

Angiopoietins are vascular factors essential for blood vessel assembly and correct organization and maturation. This study describes a novel calcium-dependent machinery activated through Angiopoietin-1/2-Tie receptor system in HUVECs monolayer. Both cytokines were found to elicit intracellular calcium mobilization. Targeting intracellular Ca2+signaling, antagonizing IP3with 2-APB or cADPR with 8Br-cADPR, was found to modulatein vitroangiogenic responses to Angiopoietins in a specific way. 2-APB and 8Br-cADPR impaired the phosphorylation of AKT and FAK induced by Ang-1 and Ang-2. On the other hand, phosphorylation of ERK1/2 and p38, as well as cell proliferation, was not affected by either inhibitor. The ability of ECs to migrate following Angs stimulation, evaluated by “scratch assay,” was reduced by either 2-APB or 8Br-cADPR following Ang-2 stimulation and only slightly affected by 2-APB in cells stimulated with Ang-1. These results identify a novel calcium-dependent machinery involved in the complex interplay regulating angiogenic processes showing that IP3- and cADPR-induced Ca2+release specifically regulates distinct Angs-mediated angiogenic steps.

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