A self-restricted CD38-connexin 43 cross-talk affects NAD+ and cyclic ADP-ribose metabolism and regulates intracellular calcium in 3T3 fibroblasts.
AuthorsBruzzone S, Franco L, Guida L, Zocchi E, Contini P, Bisso A, Usai C, De Flora A
JournalJ Biol Chem
PubMed ID11602597
'Connexin 43 (Cx43) hexameric hemichannels, recently demonstrated to mediate NAD(+) transport, functionally interact in the plasma membrane of several cells with the ectoenzyme CD38 that converts NAD(+) to the universal calcium mobilizer cyclic ADP-ribose (cADPR). Here we demonstrate that functional uncoupling between CD38 and Cx43 in CD38-transfected 3T3 murine fibroblasts ... More
Cyclic ADP-ribose and calcium-induced calcium release regulate neurotransmitter release at a cholinergic synapse of Aplysia.
'1. Presynaptic injection of cyclic ADP-ribose (cADPR), a modulator of the ryanodine receptor, increased the postsynaptic response evoked by a presynaptic spike at an identified cholinergic synapse in the buccal ganglion of Aplysia californica. 2. The statistical analysis of long duration postsynaptic responses evoked by square depolarizations of the voltage-clamped ... More
Imaging of intracellular calcium stores in single permeabilized lens cells.
AuthorsChurchill GC, Louis CF
JournalAm J Physiol
PubMed ID9950770
'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 ... More
Synthesis and characterization of antagonists of cyclic-ADP-ribose-induced Ca2+ release.
AuthorsWalseth TF, Lee HC
JournalBiochim Biophys Acta
PubMed ID8395888
'Cyclic ADP-ribose (cADPR) is a naturally-occurring metabolite of NAD+ that is as effective as inositol trisphosphate in mobilizing intracellular Ca2+. A series of analogs modified at the 8-position of the adenine group were synthesized for the investigation of the relationship between the structure of the metabolite and its Ca(2+)-mobilizing activity. ... More
Nitric oxide-induced mobilization of intracellular calcium via the cyclic ADP-ribose signaling pathway.
AuthorsWillmott N, Sethi JK, Walseth TF, Lee HC, White AM, Galione A
JournalJ Biol Chem
PubMed ID8631983
'Cyclic adenosine diphosphate ribose (cADPR) is a potent endogenous calcium-mobilizing agent synthesized from beta-NAD+ by ADP-ribosyl cyclases in sea urchin eggs and in several mammalian cells (Galione, A., and White, A. (1994) Trends Cell Biol. 4, 431 436). Pharmacological studies suggest that cADPR is an endogenous modulator of Ca2+-induced Ca2+ ... More
Vasodilation by the calcium-mobilizing messenger cyclic ADP-ribose.
AuthorsBoittin FX, Dipp M, Kinnear NP, Galione A, Evans AM
JournalJ Biol Chem
PubMed ID12486132
'In artery smooth muscle, adenylyl cyclase-coupled receptors such as beta-adrenoceptors evoke Ca(2+) signals, which open Ca(2+)-activated potassium (BK(Ca)) channels in the plasma membrane. Thus, blood pressure may be lowered, in part, through vasodilation due to membrane hyperpolarization. The Ca(2+) signal is evoked via ryanodine receptors (RyRs) in sarcoplasmic reticulum proximal ... More
Ca2+ entry induced by cyclic ADP-ribose in intact T-lymphocytes.
AuthorsGuse AH, Berg I, da Silva CP, Potter BV, Mayr GW
JournalJ Biol Chem
PubMed ID9079684
'Cyclic ADP-ribose (cADPr) is a potent Ca2+-mobilizing natural compound (Lee, H. C., Walseth, T. F., Bratt, G. T., Hayes, R. N., and Clapper, D. L. (1989) J. Biol. Chem. 264, 1608-1615) which has been shown to release Ca2+ from an intracellular store of permeabilized T-lymphocytes (Guse, A. H., Silva, C. ... More
Paracrine roles of NAD+ and cyclic ADP-ribose in increasing intracellular calcium and enhancing cell proliferation of 3T3 fibroblasts.
AuthorsFranco L, Zocchi E, Usai C, Guida L, Bruzzone S, Costa A, De Flora A
JournalJ Biol Chem
PubMed ID11274199
'CD38 is a bifunctional ectoenzyme synthesizing from NAD(+) (ADP-ribosyl cyclase) and degrading (hydrolase) cyclic ADP-ribose (cADPR), a powerful universal calcium mobilizer from intracellular stores. Recently, hexameric connexin 43 (Cx43) hemichannels have been shown to release cytosolic NAD(+) from isolated murine fibroblasts (Bruzzone, S., Guida, L., Zocchi, E., Franco, L. and ... More
The type 2 ryanodine receptor of neurosecretory PC12 cells is activated by cyclic ADP-ribose. Role of the nitric oxide/cGMP pathway.
AuthorsClementi E, Riccio M, Sciorati C, Nisticò G, Meldolesi J
JournalJ Biol Chem
PubMed ID8663443
'Of two neurosecretory PC12 cell clones that respond to NO donors and 8-bromo-cGMP with similar increases in cADP-ribose and that possess molecularly similar Ca2+ stores, only one (clone 16A) expresses the type 2 ryanodine receptor, whereas the other (clone 27) is devoid of ryanodine receptors. In PC12-16A cells, activation of ... More
Bombesin-induced cytosolic Ca2+ spiking in pancreatic acinar cells depends on cyclic ADP-ribose and ryanodine receptors.
AuthorsBurdakov D, Cancela JM, Petersen OH
JournalCell Calcium
PubMed ID11162858
'Different hormones and neurotransmitters, using Ca2+ as their intracellular messenger, can generate specific cytosolic Ca2+ signals in different parts of a cell. In mouse pancreatic acinar cells, cytosolic Ca2+ oscillations are triggered by activation of acetylcholine (ACh), cholecystokinin (CCK) and bombesin receptors. Low concentrations of these three agonists all induce ... More
Preparation of cyclic ADP-ribose antagonists and caged cyclic ADP-ribose.
AuthorsWalseth TF, Aarhus R, Gurnack ME, Wong L, Breitinger HG, Gee KR, Lee HC
JournalMethods Enzymol
PubMed ID9211325
Cyclic ADP-ribose: a new member of a super family of signalling cyclic nucleotides.
AuthorsLee HC
JournalCell Signal
PubMed ID7857763
Cyclic nucleotides are second messengers exerting their cellular effects mainly through protein phosphorylation. A new member of this family, cyclic ADP-ribose, is involved, instead, in mediating mobilization of Ca+2 from internal stores. The structure of this nucleotide has now been determined by X-ray crystallography and accumulating evidence indicates it may ... More
Cyclic ADP-ribose: a calcium mobilizing metabolite of NAD+.
AuthorsLee HC
JournalMol Cell Biochem
PubMed ID7898468
Mobilization of Ca+2 from intracellular stores is a signalling mechanism that is of fundamental importance to many cellular processes. It is mediated by two major mechanisms, the inositol 1,4,5-trisphosphate pathway and the Ca+2-induced Ca+2 release process. A naturally occurring metabolite of NAD+ called cyclic ADP-ribose has been discovered recently and ... More
Bioorganic chemistry of cyclic ADP-ribose (cADPR).
AuthorsZhang FJ, Gu QM, Sih CJ
JournalBioorg Med Chem
PubMed ID10400320
The objective of this brief review is to present an overview of the bioorganic chemistry of cyclic-ADP-ribose (cADPR) with special emphasis on the methodology used for the synthesis of analogues of cADPR. New structural analogues of cADPR can be prepared using either the biomimetic method or ADP-ribosyl cyclase from Aplysia ... More
Effects of 1-methyladenine on nuclear Ca2+ transients and meiosis resumption in starfish oocytes are mimicked by the nuclear injection of inositol 1,4,5-trisphosphate and cADP-ribose.
AuthorsSantella L, Kyozuka K
JournalCell Calcium
PubMed ID9232348
The treatment of prophase-arrested starfish oocytes with the hormone 1-methyladenine (1-MA) induces the elevation of Ca2+ in both the cytoplasm and the germinal vesicle (nucleus), and is followed by the resumption of meiosis. The injection of the modulators of the intracellular Ca2+ channels inositol 1,4,5-trisphosphate (InsP3) or cyclic adenosine diphosphate ... More
Coordination of agonist-induced Ca2+-signalling patterns by NAADP in pancreatic acinar cells.
AuthorsCancela JM, Churchill GC, Galione A
JournalNature
PubMed ID10078532
Many hormones and neurotransmitters evoke Ca2+ release from intracellular stores, often triggering agonist-specific signatures of intracellular Ca2+ concentration. Inositol trisphosphate (InsP3) and cyclic adenosine 5'-diphosphate-ribose (cADPR) are established Ca2+-mobilizing messengers that activate Ca2+ release through intracellular InsP3 and ryanodine receptors, respectively. However, in pancreatic acinar cells, neither messenger can explain ... More
Caged cyclic ADP-ribose. Synthesis and use.
AuthorsAarhus R, Gee K, Lee HC
JournalJ Biol Chem
PubMed ID7706323
Cyclic ADP-ribose (cADPR) is a recently discovered cyclic nucleotide with Ca2+ mobilizing activity. Caged cADPR was synthesized by reacting cADPR with 2-nitrophenethyldiazoethane. Elemental analyses, 1H NMR, and extinction coefficient measurements indicate that the product contains only one caging group. Anion exchange high pressure liquid chromatography separated caged cADPR into two ... More
Cyclic ADP-ribose and inositol 1,4,5-trisphosphate as alternate second messengers for intracellular Ca2+ mobilization in normal and diabetic beta-cells.
AuthorsTakasawa S, Akiyama T, Nata K, Kuroki M, Tohgo A, Noguchi N, Kobayashi S, Kato I, Katada T, Okamoto H
JournalJ Biol Chem
PubMed ID9446548
Intracellular Ca2+ mobilization occurs in a variety of cellular processes and is mediated by two major systems, the inositol 1,4, 5-trisphosphate (IP3) and cyclic ADP-ribose (cADPR) systems. cADPR has been proposed to be a second messenger for insulin secretion induced by glucose in pancreatic beta-cells (Takasawa, S., Nata, K., Yonekura, ... More
Role of cyclic ADP-ribose in the regulation of [Ca2+]i in porcine tracheal smooth muscle.
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 beta-escin, and real-time confocal microscopy was used to examine changes in ... More
Expression of CD38 increases intracellular calcium concentration and reduces doubling time in HeLa and 3T3 cells.
AuthorsZocchi E, Daga A, Usai C, Franco L, Guida L, Bruzzone S, Costa A, Marchetti C, De Flora A
JournalJ Biol Chem
PubMed ID9525901
CD38 is a bifunctional ectoenzyme, predominantly expressed on hematopoietic cells during differentiation, that catalyzes the synthesis (cyclase) and the degradation (hydrolase) of cyclic ADP-ribose (cADPR), a powerful calcium mobilizer from intracellular stores. Due to the well established role of calcium levels in the regulation of apoptosis, proliferation, and differentiation, the ... More
A cytosolic sperm protein factor mobilizes Ca2+ from intracellular stores by activating multiple Ca2+ release mechanisms independently of low molecular weight messengers.
AuthorsGalione A, Jones KT, Lai FA, Swann K
JournalJ Biol Chem
PubMed ID9360959
Ca2+ oscillations can be induced in mammalian eggs and somatic cells by microinjection of a cytosolic sperm protein factor. The nature of the sperm factor-induced Ca2+ signaling was investigated by adding sperm protein extracts to homogenates of sea urchin eggs, which contain multiple classes of Ca2+ release mechanisms. We show ... More
Spatial control of Ca2+ signaling by nicotinic acid adenine dinucleotide phosphate diffusion and gradients.
AuthorsChurchill GC, Galione A
JournalJ Biol Chem
PubMed ID11006280
Intracellular Ca(2+) is able to control numerous cellular responses through complex spatiotemporal organization. Ca(2+) waves mediated by inositol trisphosphate or ryanodine receptors propagate by Ca(2+)-induced Ca(2+) release and therefore do not have an absolute requirement for a gradient in either inositol trisphosphate or cyclic ADP-ribose, respectively. In contrast, we report ... More
A pivotal role for cADPR-mediated Ca2+ signaling: regulation of endothelin-induced contraction in peritubular smooth muscle cells.
AuthorsBarone F, Genazzani AA, Conti A, Churchill GC, Palombi F, Ziparo E, Sorrentino V, Galione A, Filippini A
JournalFASEB J
PubMed ID11978734
cADPR, a potent calcium-mobilizing intracellular messenger synthesized by ADP-ribosyl cyclases regulates openings of ryanodine receptors (RyR). Here we report that in the rat testis, a functional cADPR Ca2+ release system is essential for the contractile response of peritubular smooth muscle cells (PSMC) to endothelin (ET). We previously showed that this ... More
Insulin exocytosis and glucose-mediated increase in cytoplasmic free Ca2+ concentration in the pancreatic beta-cell are independent of cyclic ADP-ribose.
AuthorsWebb DL, Islam MS, Efanov AM, Brown G, Köhler M, Larsson O, Berggren PO
JournalJ Biol Chem
PubMed ID8702579
Stimulation of pancreatic beta-cells by glucose gives rise to an increase in the cytoplasmic free calcium concentration ([Ca2+]i) and exocytosis of insulin. Cyclic adenosine 5'-diphosphate ribose (cADPR), a metabolite of beta-NAD+, has been reported to increase [Ca2+]i in pancreatic beta-cells by releasing Ca2+ from inositol 1,4,5-trisphosphate-insensitive intracellular stores. In the ... More
Localization of the cyclic ADP-ribose-dependent calcium signaling pathway in hepatocyte nucleus.
AuthorsKhoo KM, Han MK, Park JB, Chae SW, Kim UH, Lee HC, Bay BH, Chang CF
JournalJ Biol Chem
PubMed ID10818108
CD38 is a type II transmembrane glycoprotein found on both hematopoietic and non-hematopoietic cells. It is known for its involvement in the metabolism of cyclic ADP-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate, two nucleotides with calcium mobilizing activity independent of inositol trisphosphate. It is generally believed that CD38 is ... More
Cyclic 3-deaza-adenosine diphosphoribose: a potent and stable analog of cyclic ADP-ribose.
AuthorsWong L, Aarhus R, Lee HC, Walseth TF
JournalBiochim Biophys Acta
PubMed ID10564770
Cyclic 3-deaza-adenosine diphosphoribose (3-deaza-cADPR), an analog of cyclic adenosine diphosphoribose (cADPR) was synthesized. 3-deaza-cADPR differs from cADPR by only the substitution of carbon for nitrogen at the 3-position of the purine ring. Similar to cADPR, the analog has potent calcium releasing activity in sea urchin egg homogenates and was able ... More
An antagonist of cADP-ribose inhibits arrhythmogenic oscillations of intracellular Ca2+ in heart cells.
AuthorsRakovic S, Cui Y, Iino S, Galione A, Ashamu GA, Potter BV, Terrar DA
JournalJ Biol Chem
PubMed ID10364226
Oscillations of Ca2+ in heart cells are a major underlying cause of important cardiac arrhythmias, and it is known that Ca2+-induced release of Ca2+ from intracellular stores (the sarcoplasmic reticulum) is fundamental to the generation of such oscillations. There is now evidence that cADP-ribose may be an endogenous regulator of ... More
Role of cyclic ADP-ribose in ATP-activated potassium currents in alveolar macrophages.
AuthorsEbihara S, Sasaki T, Hida W, Kikuchi Y, Oshiro T, Shimura S, Takasawa S, Okamoto H, Nishiyama A, Akaike N, Shirato K
JournalJ Biol Chem
PubMed ID9188506
There is growing evidence that extracellular ATP causes a dramatic change in the membrane conductance of a variety of inflammatory cells. In the present study, using the nystatin perforated patch recording configuration, we found that ATP (0.3-30 microM) induced a transient outward current in a concentration-dependent manner and that the ... More
Effects of photoreleased cADP-ribose on calcium transients and calcium sparks in myocytes isolated from guinea-pig and rat ventricle.
AuthorsCui Y, Galione A, Terrar DA
JournalBiochem J
PubMed ID10455010
Actions of photoreleased cADP-ribose (cADPR), a novel regulator of calcium-induced calcium release (CICR) from ryanodine-sensitive stores, were investigated in cardiac myocytes. Photoreleased cADPR caused an increase in the magnitude of whole-cell calcium transients studied in mammalian cardiac ventricular myocytes (both guinea-pig and rat) using confocal microscopy). Approx. 15 s was ... More
Agonist-stimulated cyclic ADP ribose. Endogenous modulator of Ca(2+)-induced Ca2+ release in intestinal longitudinal muscle.
AuthorsKuemmerle JF, Makhlouf GM
JournalJ Biol Chem
PubMed ID7592718
We have previously shown that agonist-induced Ca2+ mobilization in intestinal longitudinal muscle is mediated by ryanodine-sensitive, inositol 1,4,5-trisphosphate-insensitive sacroplasmic Ca2+ channels. Ca2+ release via these channels is triggered by agonist-stimulated Ca2+ influx and results in Ca(2+)-induced Ca2+ release. The present study examined whether cyclic ADP-ribose (cADPR) is synthesized in response ... More
Mechanisms of calcium signaling by cyclic ADP-ribose and NAADP.
AuthorsLee HC
JournalPhysiol Rev
PubMed ID9354813
Cells possess various mechanisms for transducing external signals to intracellular responses. The discovery of inositol 1,4,5-trisphosphate (IP3) as a messenger for mobilizing internal Ca2+ stores has centralized Ca2+ mobilization among signaling mechanisms. Results reviewed in this article establish that, in addition to IP3, the internal Ca2+ stores can be mobilized ... More