scholarly journals Cyclic ADP-ribose increases Ca2+ removal in smooth muscle

2003 ◽  
Vol 116 (21) ◽  
pp. 4291-4306 ◽  
Author(s):  
K. N. Bradley
Keyword(s):  
Smooth Muscle ◽  
Cyclic Adp Ribose

scholarly journals Altered CD38/Cyclic ADP-Ribose Signaling Contributes to the Asthmatic Phenotype

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Joseph A. Jude ◽  
Mythili Dileepan ◽  
Reynold A. Panettieri ◽  
Timothy F. Walseth ◽  
Mathur S. Kannan
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Intracellular Calcium ◽  
Airway Smooth Muscle ◽  
Airway Hyperresponsiveness ◽  
Map Kinases ◽  
Muscle Cells ◽  
Airway Smooth Muscle Cells ◽  
Cd38 Expression ◽  
Cyclic Adp Ribose

CD38 is a transmembrane glycoprotein expressed in airway smooth muscle cells. The enzymatic activity of CD38 generates cyclic ADP-ribose from β-NAD. Cyclic ADP-ribose mobilizes intracellular calcium during activation of airway smooth muscle cells by G-protein-coupled receptors through activation of ryanodine receptor channels in the sarcoplasmic reticulum. Inflammatory cytokines that are implicated in asthma upregulate CD38 expression and increase the calcium responses to contractile agonists in airway smooth muscle cells. The augmented intracellular calcium responses following cytokine exposure of airway smooth muscle cells are inhibited by an antagonist of cyclic ADP-ribose. Airway smooth muscle cells from CD38 knockout mice exhibit attenuated intracellular calcium responses to agonists, and these mice have reduced airway response to inhaled methacholine. CD38 also contributes to airway hyperresponsiveness as shown in mouse models of allergen or cytokine-induced inflammatory airway disease. In airway smooth muscle cells obtained from asthmatics, the cytokine-induced CD38 expression is significantly enhanced compared to expression in cells from nonasthmatics. This differential induction of CD38 expression in asthmatic airway smooth muscle cells stems from increased activation of MAP kinases and transcription through NF-κB, and altered post-transcriptional regulation through microRNAs. We propose that increased capacity for CD38 signaling in airway smooth muscle in asthma contributes to airway hyperresponsiveness.

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.

Regulation of KCa-channel activity by cyclic ADP-ribose and ADP-ribose in coronary arterial smooth muscle

1998 ◽  
Vol 275 (3) ◽  
pp. H1002-H1010 ◽  
Author(s):  
Pin-Lan Li ◽  
Ai-Ping Zou ◽  
William B. Campbell
Keyword(s):  
Smooth Muscle ◽  
Time Course ◽  
Control Level ◽  
Internal Surface ◽  
Threshold Concentration ◽  
Dependent Manner ◽  
Channel Activity ◽  
Arterial Smooth Muscle ◽  
Concentration Dependent Manner ◽  
Cyclic Adp Ribose

The enzymatic pathway responsible for the production and metabolism of cyclic ADP-ribose (cADP-R) in small bovine coronary arteries was characterized, and the role of cADP-R and ADP-ribose (ADP-R) in the regulation of the activity of large-conductance Ca2+-activated K+(KCa) channels was determined in vascular smooth muscle cells (SMC) prepared from these vessels. We found that cADP-R and ADP-R were produced when the coronary arterial homogenates were incubated with 1 mM β-NAD. The time course of the enzyme reactions showed that the maximal conversion rate (1.37 ± 0.03 nmol ⋅ min−1 ⋅ mg protein−1) of β-NAD to cADP-R was reached after 3 min of incubation. As incubation time was prolonged, the production of ADP-R was increased to a maximal rate of 3.66 ± 0.03 nmol ⋅ min−1 ⋅ mg protein−1, whereas cADP-R production decreased. Incubation of the homogenate with cADP-R produced a time-dependent increase in the synthesis of ADP-R. Comparison of coronary arterial microsomes with cytosols shows that the production of both cADP-R and ADP-R in microsomes was significantly greater. In excised inside-out membrane patches of single coronary SMC, the KCa channels were activated when β-NAD, the precursor for both cADP-R and ADP-R, was applied to the internal surface. This effect of β-NAD may be associated with the production of ADP-R, because the KCa-channel activity was increased by ADP-R in a concentration-dependent manner. The open-state probability of the KCa channels increased from a control level of 0.08 ± 0.03 to 0.17 ± 0.05 even at the lowest ADP-R concentration (0.1 μM) studied. However, cADP-R reduced the KCa-channel activity, and the threshold concentration of cADP-R that decreased the average channel activity of the KCa channels was 1 μM. These results provide evidence that cADP-R is produced and metabolized in the coronary arterial smooth muscle and that a cADP-R/ADP-R pathway participates in the control of the KCa-channel activity in vascular SMC.

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 Cyclic ADP-ribose requires CD38 to regulate the release of ATP in visceral smooth muscle

FEBS Journal ◽  
2011 ◽  
Vol 278 (17) ◽  
pp. 3095-3108 ◽  
Author(s):  
Leonie Durnin ◽  
Violeta N. Mutafova-Yambolieva
Keyword(s):  
Smooth Muscle ◽  
Cyclic Adp Ribose ◽  
Visceral Smooth Muscle

Emerging role of cyclic ADP-ribose (cADPR) in smooth muscle

2005 ◽  
Vol 105 (2) ◽  
pp. 189-207 ◽  
Author(s):  
Ni Bai ◽  
Hon Cheung Lee ◽  
Ismail Laher
Keyword(s):  
Smooth Muscle ◽  
Cyclic Adp Ribose

Cyclic ADP-Ribose Contributes to Contraction and Ca2+ Release by M1 Muscarinic Receptor Activation in Coronary Arterial Smooth Muscle

2003 ◽  
Vol 40 (1) ◽  
pp. 28-36 ◽  
Author(s):  
Zhi-Dong Ge ◽  
David X. Zhang ◽  
Ya-Fei Chen ◽  
Fu-Xian Yi ◽  
Ai-Ping Zou ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Muscarinic Receptor ◽  
Receptor Activation ◽  
Arterial Smooth Muscle ◽  
Cyclic Adp Ribose

CD38-deficient mice have reduced airway hyperresponsiveness following IL-13 challenge

2006 ◽  
Vol 291 (6) ◽  
pp. L1286-L1293 ◽  
Author(s):  
Alonso G. P. Guedes ◽  
Jaime Paulin ◽  
Laura Rivero-Nava ◽  
Hirohito Kita ◽  
Frances E. Lund ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Airway Hyperresponsiveness ◽  
Isometric Force ◽  
Airway Disease ◽  
Smooth Muscle Contractility ◽  
Mechanically Ventilated ◽  
Transmembrane Glycoprotein ◽  
Cyclic Adp Ribose ◽  
Regulatory Effects

The transmembrane glycoprotein CD38 in airway smooth muscle is the source of cyclic-ADP ribose, an intracellular calcium-releasing molecule, and is subject to regulatory effects of cytokines such as interleukin (IL)-13, a cytokine implicated in asthma. We investigated the role of CD38 in airway hyperresponsiveness using a mouse model of IL-13-induced airway disease. Wild-type (WT) and CD38-deficient (CD38KO) mice were intranasally challenged with 5 μg of IL-13 three times on alternate days under isoflurane anesthesia. Lung resistance (RL) in response to inhaled methacholine was measured 24 h after the last challenge in pentobarbital-anesthetized, tracheostomized, and mechanically ventilated mice. Bronchoalveolar cytokines, bronchoalveolar and parenchymal inflammation, and smooth muscle contractility and relaxation using tracheal segments were also evaluated. Changes in methacholine-induced RL were significantly greater in the WT than in the CD38KO mice following intranasal IL-13 challenges. Airway reactivity after IL-13 exposure, as measured by the slope of the methacholine dose-response curve, was significantly higher in the WT than in the CD38KO mice. The rate of isometric force generation in tracheal segments (e.g., smooth muscle reactivity) was greater in the WT than in the CD38KO mice following incubation with IL-13. IL-13 treatment reduced isoproterenol-induced relaxations to similar magnitudes in tracheal segments obtained from WT and CD38KO mice. Both WT and CD38KO mice developed significant bronchoalveolar and parenchymal inflammation after IL-13 challenges compared with naïve controls. The results indicate that CD38 contributes to airway hyperresponsiveness in lungs exposed to IL-13 at least partly by increasing airway smooth muscle reactivity to contractile agonists.

scholarly journals Downregulation of miR-140-3p Contributes to Upregulation of CD38 Protein in Bronchial Smooth Muscle Cells

2020 ◽  
Vol 21 (21) ◽  
pp. 7982
Author(s):  
Yoshihiko Chiba ◽  
Mayumi Matsumoto ◽  
Motohiko Hanazaki ◽  
Hiroyasu Sakai
Keyword(s):  
Smooth Muscle ◽  
Protein Expression ◽  
Smooth Muscles ◽  
Muscle Contractility ◽  
Bronchial Smooth Muscle ◽  
Smooth Muscle Contractility ◽  
Airway Diseases ◽  
Cyclic Adp Ribose ◽  
Bronchial Smooth Muscle Cells

In allergic bronchial asthma, an increased smooth muscle contractility of the airways is one of the causes of the airway hyperresponsiveness (AHR). Increasing evidence also suggests a possible involvement of microRNAs (miRNAs) in airway diseases, including asthma, although their roles in function and pathology largely unknown. The current study aimed to determine the role of a miRNA, miR-140-3p, in the control of protein expression of CD38, which is believed to regulate the contraction of smooth muscles, including the airways. In bronchial smooth muscles (BSMs) of the mice that were actively sensitized and repeatedly challenged with ovalbumin antigen, an upregulation of CD38 protein concurrently with a significant reduction of miR-140-3p was observed. In cultured human BSM cells (hBSMCs), transfection with a synthetic miR-140-3p inhibitor caused an increase in CD38 protein, indicating that its basal protein expression is regulated by endogenous miR-140-3p. Treatment of the hBSMCs with interleukin-13 (IL-13), an asthma-related cytokine, caused both an upregulation of CD38 protein and a downregulation of miR-140-3p. Transfection of the hBSMCs with miR-140-3p mimic inhibited the CD38 protein upregulation induced by IL-13. On the other hand, neither a CD38 product cyclic ADP-ribose (cADPR) nor its antagonist 8-bromo-cADPR had an effect on the BSM contraction even in the antigen-challenged mice. Taken together, the current findings suggest that the downregulation of miR-140-3p induced by IL-13 might cause an upregulation of CD38 protein in BSM cells of the disease, although functional and pathological roles of the upregulated CD38 are still unclear.

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