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CD38-Cyclic ADP-Ribose-Mediated Calcium Signaling in Airway Myocytes

  • Deepak A. Deshpande
  • Alonso Guedes
  • Mythili Dileepan
  • Timothy F. Walseth
  • Mathur S. KannanEmail author
Chapter

Abstract

Nicotinamide adenine dinucleotide (NAD) metabolites, cyclic ADP-ribose (cADPR), and nicotinic acid adenine dinucleotide phosphate (NAADP) have been identified as calcium-releasing second messengers. In smooth muscle including that of airways, cADPR plays a vital role in the dynamic regulation of intracellular calcium and contraction. CD38, a 45 kDa bifunctional transmembrane protein, possesses enzymatic activities (ADP-ribosyl cyclase and cADPR hydrolase) necessary for the synthesis and degradation of cADPR. Together, CD38 and cADPR form a signaling cascade in agonist-induced calcium elevation in airway smooth muscle (ASM) cells similar to well-established phospholipase C and inositol trisphosphate (PLC/IP3) pathway. CD38/cADPR is considered an endogenous activator of calcium release from the sarcoplasmic reticulum via ryanodine receptor channels. Most importantly, findings from ex vivo and in vivo studies have established the contribution of CD38/cADPR-mediated calcium release to the regulation of contractile responsiveness of airways and respiratory function. CD38 expression is regulated by inflammatory cytokines, microRNAs, and exogenous drugs such as corticosteroids. Changes in CD38 expression and cADPR production have significant consequences in ASM functions and also contribute to hyperresponsiveness seen during airway inflammatory conditions such as asthma. This chapter describes numerous studies that have established signaling, functional, and pathophysiological roles of CD38/cADPR in ASM.

Keywords

CD38 cADPR Cyclase Cytokine miRNA 

References

  1. 1.
    Ay B, Prakash YS, Pabelick CM and Sieck GC. Store-operated Ca2+ entry in porcine airway smooth muscle. Am J Physiol Lung Cell Mol Physiol 286: L909–L917, 2004.PubMedCrossRefGoogle Scholar
  2. 2.
    Bai Y, Zhang M and Sanderson MJ. Contractility and Ca2+ signaling of smooth muscle cells in different generations of mouse airways. Am J Respir Cell Mol Biol 36: 122–130, 2007.PubMedCrossRefGoogle Scholar
  3. 3.
    Barone F, Genazzani AA, Conti A, Churchill GC, Palombi F, Ziparo E, Sorrentino V, Galione A and Filippini A. A pivotal role for cADPR-mediated Ca2+ signaling: regulation of endothelin-induced contraction in peritubular smooth muscle cells. FASEB J 16: 697–705, 2002.PubMedCrossRefGoogle Scholar
  4. 4.
    Bergner A and Sanderson MJ. Acetylcholine-induced calcium signaling and contraction of airway smooth muscle cells in lung slices. J Gen Physiol 119: 187–198, 2002.PubMedCrossRefGoogle Scholar
  5. 5.
    Billington CK and Penn RB. Signaling and regulation of G protein-coupled receptors in airway smooth muscle. Respir Res 4: 2, 2003.PubMedGoogle Scholar
  6. 6.
    Chilvers ER, Batty IH, Barnes PJ and Nahorski SR. Formation of inositol polyphosphates in airway smooth muscle after muscarinic receptor stimulation. J Pharmacol Exp Ther 252: 786–791, 1990.PubMedGoogle Scholar
  7. 7.
    Chilvers ER, Lynch BJ and Challiss RA. Phosphoinositide metabolism in airway smooth muscle. Pharmacol Ther 62: 221–245, 1994.PubMedCrossRefGoogle Scholar
  8. 8.
    Cockayne DA, Muchamuel T, Grimaldi JC, Muller-Steffner H, Randall TD, Lund FE, Murray R, Schuber F and Howard MC. Mice deficient for the ecto-nicotinamide adenine dinucleotide glycohydrolase CD38 exhibit altered humoral immune responses. Blood 92: 1324–33, 1998.PubMedGoogle Scholar
  9. 9.
    Deshpande DA, Dogan S, Walseth TF, Miller SM, Amrani Y, Panettieri RA and Kannan MS. Modulation of calcium signaling by interleukin-13 in human airway smooth muscle: role of CD38/cyclic adenosine diphosphate ribose pathway. Am J Respir Cell Mol Biol 31: 36–42, 2004.PubMedCrossRefGoogle Scholar
  10. 10.
    Deshpande DA and Penn RB. Targeting G protein-coupled receptor signaling in asthma. Cell Signal 18: 2105–2120, 2006.PubMedCrossRefGoogle Scholar
  11. 11.
    Deshpande DA, Walseth TF, Panettieri RA and Kannan MS. CD38/cyclic ADP-ribose-mediated Ca2+ signaling contributes to airway smooth muscle hyper-responsiveness. FASEB J 17: 452–4, 2003.PubMedGoogle Scholar
  12. 12.
    Deshpande DA, Wang WC, McIlmoyle EL, Robinett KS, Schillinger RM, An SS, Sham JS and Liggett SB. Bitter taste receptors on airway smooth muscle bronchodilate by localized calcium signaling and reverse obstruction. Nat Med 16: 1299–1304, 2010.PubMedCrossRefGoogle Scholar
  13. 13.
    Deshpande DA, White TA, Dogan S, Walseth TF, Panettieri RA and Kannan MS. CD38/cyclic ADP-ribose signaling: role in the regulation of calcium homeostasis in airway smooth muscle. Am J Physiol Lung Cell Mol Physiol 288: L773–L788, 2005.PubMedCrossRefGoogle Scholar
  14. 14.
    Deshpande DA, White TA, Guedes AG, Milla C, Walseth TF, Lund FE and Kannan MS. Altered airway responsiveness in CD38-deficient mice. Am J Respir Cell Mol Biol 32: 149–156, 2005.PubMedCrossRefGoogle Scholar
  15. 15.
    Dipp M and Evans AM. Cyclic ADP-ribose is the primary trigger for hypoxic pulmonary vasoconstriction in the rat lung in situ. Circ Res 89: 77–83, 2001.PubMedCrossRefGoogle Scholar
  16. 16.
    Franco L, Bruzzone S, Song P, Guida L, Zocchi E, Walseth TF, Crimi E, Usai C, De Flora A and Brusasco V. Extracellular cyclic ADP-ribose potentiates ACh-induced contraction in bovine tracheal smooth muscle. Am J Physiol Lung Cell Mol Physiol 280: L98–L106, 2001.PubMedGoogle Scholar
  17. 17.
    Gally F, Hartney JM, Janssen WJ and Perraud AL. CD38 plays a dual role in allergen-induced airway hyperresponsiveness. Am J Respir Cell Mol Biol 40: 433–442, 2009.PubMedCrossRefGoogle Scholar
  18. 18.
    Ge ZD, Zhang DX, Chen YF, Yi FX, Zou AP, Campbell WB and Li PL. Cyclic ADP-ribose contributes to contraction and Ca2+ release by M1 muscarinic receptor activation in coronary arterial smooth muscle. J Vasc Res 40: 28–36, 2003.PubMedCrossRefGoogle Scholar
  19. 19.
    Gosling M, Poll C and Li S. TRP channels in airway smooth muscle as therapeutic targets. Naunyn Schmiedebergs Arch Pharmacol 371: 277–284, 2005.PubMedCrossRefGoogle Scholar
  20. 20.
    Guedes AG, Jude JA, Paulin J, Kita H, Lund FE and Kannan MS. Role of CD38 in TNF-alpha-induced airway hyperresponsiveness. Am J Physiol Lung Cell Mol Physiol 294: L290–L299, 2008.PubMedCrossRefGoogle Scholar
  21. 21.
    Guedes AG, Paulin J, Rivero-Nava L, Kita H, Lund FE and Kannan MS. CD38-deficient mice have reduced airway hyperresponsiveness following IL-13 challenge. Am J Physiol Lung Cell Mol Physiol 291: L1286–L1293, 2006.PubMedCrossRefGoogle Scholar
  22. 22.
    Higashida H, Egorova A, Higashida C, Zhong ZG, Yokoyama S, Noda M and Zhang JS. Sympathetic potentiation of cyclic ADP-ribose formation in rat cardiac myocytes. J Biol Chem 274: 33348–54, 1999.PubMedCrossRefGoogle Scholar
  23. 23.
    Hirota S, Helli P and Janssen LJ. Ionic mechanisms and Ca2+ handling in airway smooth muscle. Eur Respir J 30: 114–133, 2007.PubMedCrossRefGoogle Scholar
  24. 24.
    Holtzman MJ. Asthma as a chronic disease of the innate and adaptive immune systems responding to viruses and allergens. J Clin Invest 122: 2741–2748, 2012.PubMedCrossRefGoogle Scholar
  25. 25.
    Jain D, Keslacy S, Tliba O, Cao Y, Kierstein S, Amin K, Panettieri RA, Jr., Haczku A and Amrani Y. Essential role of IFNbeta and CD38 in TNFalpha-induced airway smooth muscle hyper-responsiveness. Immunobiology 213: 499–509, 2008.PubMedCrossRefGoogle Scholar
  26. 26.
    Janssen LJ. Ionic mechanisms and Ca(2+) regulation in airway smooth muscle contraction: do the data contradict dogma? Am J Physiol Lung Cell Mol Physiol 282: 1161–78, 2002.CrossRefGoogle Scholar
  27. 27.
    Jude JA, Dileepan M, Subramanian S, Solway J, Panettieri RA, Jr., Walseth TF and Kannan MS. miR-140-3p regulation of TNF-alpha-induced CD38 expression in human airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 303: L460–L468, 2012.PubMedCrossRefGoogle Scholar
  28. 28.
    Jude JA, Panettieri RA, Jr., Walseth TF and Kannan MS. TNF-alpha regulation of CD38 expression in human airway smooth muscle: role of MAP kinases and NF-kappaB. Adv Exp Med Biol 691: 449–459, 2011.PubMedCrossRefGoogle Scholar
  29. 29.
    Jude JA, Solway J, Panettieri RA, Jr., Walseth TF and Kannan MS. Differential induction of CD38 expression by TNF-{alpha} in asthmatic airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 299: L879–L890, 2010.PubMedCrossRefGoogle Scholar
  30. 30.
    Jude JA, Tirumurugaan KG, Kang BN, Panettieri RA, Walseth TF and Kannan MS. Regulation of CD38 expression in human airway smooth muscle cells: role of class I phosphatidylinositol 3 kinases. Am J Respir Cell Mol Biol 47: 427–435, 2012.PubMedCrossRefGoogle Scholar
  31. 31.
    Kang BN, Deshpande DA, Tirumurugaan KG, Panettieri RA, Walseth TF and Kannan MS. Adenoviral mediated anti-sense CD38 attenuates TNF-alpha-induced changes in calcium homeostasis of human airway smooth muscle cells. Can J Physiol Pharmacol 83: 799–804, 2005.PubMedCrossRefGoogle Scholar
  32. 32.
    Kang BN, Tirumurugaan KG, Deshpande DA, Amrani Y, Panettieri RA, Walseth TF and Kannan MS. Transcriptional regulation of CD38 expression by tumor necrosis factor-alpha in human airway smooth muscle cells: role of NF-kappaB and sensitivity to glucocorticoids. FASEB J 20: 1000–1002, 2006.PubMedCrossRefGoogle Scholar
  33. 33.
    Kip SN, Smelter M, Iyanoye A, Chini EN, Prakash YS, Pabelick CM and Sieck GC. Agonist-induced cyclic ADP ribose production in airway smooth muscle. Arch Biochem Biophys 452: 102–107, 2006.PubMedCrossRefGoogle Scholar
  34. 34.
    Kotlikoff MI. Calcium-induced calcium release in smooth muscle: the case for loose coupling. Prog Biophys Mol Biol 83: 171–91, 2003.PubMedCrossRefGoogle Scholar
  35. 35.
    Kuemmerle JF and Makhlouf GM. Agonist-stimulated cyclic ADP ribose. Endogenous modulator of Ca(2+)-induced Ca2+ release in intestinal longitudinal muscle. Journal of Biological Chemistry 270: 25488–94, 1995.PubMedCrossRefGoogle Scholar
  36. 36.
    Kuemmerle JF, Murthy KS and Makhlouf GM. Longitudinal smooth muscle of the mammalian intestine. A model for Ca2+ signaling by cADPR. Cell Biochem Biophys 28: 31–44, 1998.PubMedCrossRefGoogle Scholar
  37. 37.
    Lanner JT, Georgiou DK, Joshi AD and Hamilton SL. Ryanodine receptors: structure, expression, molecular details, and function in calcium release. Cold Spring Harb Perspect Biol 2: a003996, 2010.PubMedCrossRefGoogle Scholar
  38. 38.
    Lee HC, Aarhus R and Graeff RM. Sensitization of calcium-induced calcium release by cyclic ADP-ribose and calmodulin. Journal of Biological Chemistry 270: 9060–6, 1995.PubMedCrossRefGoogle Scholar
  39. 39.
    Lee HC, Galione A and Walseth TF. Cyclic ADP-ribose: metabolism and calcium mobilizing function. Vitam Horm 48: 199–257, 1994.PubMedCrossRefGoogle Scholar
  40. 40.
    Li PL, Tang WX, Valdivia HH, Zou AP and Campbell WB. cADP-ribose activates reconstituted ryanodine receptors from coronary arterial smooth muscle. Am J Physiol Heart Circ Physiol 280: 208–15, 2001.Google Scholar
  41. 41.
    Lifshitz LM, Carmichael JD, Lai FA, Sorrentino V, Bellve K, Fogarty KE and ZhuGe R. Spatial organization of RYRs and BK channels underlying the activation of STOCs by Ca(2+) sparks in airway myocytes. J Gen Physiol 138: 195–209, 2011.PubMedCrossRefGoogle Scholar
  42. 42.
    Malavasi F, Deaglio S, Funaro A, Ferrero E, Horenstein AL, Ortolan E, Vaisitti T and Aydin S. Evolution and function of the ADP ribosyl cyclase/CD38 gene family in physiology and pathology. Physiol Rev 88: 841–886, 2008.PubMedCrossRefGoogle Scholar
  43. 43.
    Mizuta K, Xu D, Pan Y, Comas G, Sonett JR, Zhang Y, Panettieri RA, Jr., Yang J and Emala CW, Sr. GABAA receptors are expressed and facilitate relaxation in airway smooth muscle. Am J Physiol Lung Cell Mol Physiol 294: L1206–L1216, 2008.PubMedCrossRefGoogle Scholar
  44. 44.
    Noguchi N, Takasawa S, Nata K, Tohgo A, Kato I, Ikehata F, Yonekura H and Okamoto H. Cyclic ADP-ribose binds to FK506-binding protein 12.6 to release Ca2+ from islet microsomes. Journal of Biological Chemistry 272: 3133–6, 1997.PubMedCrossRefGoogle Scholar
  45. 45.
    Osawa Y, Xu D, Sternberg D, Sonett JR, D’Armiento J, Panettieri RA and Emala CW. Functional expression of the GABAB receptor in human airway smooth muscle. Am J Physiol Lung Cell Mol Physiol 291: L923–L931, 2006.PubMedCrossRefGoogle Scholar
  46. 46.
    Ozawa T. Ryanodine-sensitive Ca(2+) release mechanism of rat pancreatic acinar cells is modulated by calmodulin. Biochimica et Biophysica Acta 1452: 254–62, 1999.PubMedCrossRefGoogle Scholar
  47. 47.
    Ozawa T and Nishiyama A. Characterization of ryanodine-sensitive Ca2+ release from microsomal vesicles of rat parotid acinar cells: regulation by cyclic ADP-ribose. Journal of Membrane Biology 156: 231–9, 1997.PubMedCrossRefGoogle Scholar
  48. 48.
    Partida-Sanchez S, Cockayne DA, Monard S, Jacobson EL, Oppenheimer N, Garvy B, Kusser K, Goodrich S, Howard M, Harmsen A, Randall TD and Lund FE. Cyclic ADP-ribose production by CD38 regulates intracellular calcium release, extracellular calcium influx and chemotaxis in neutrophils and is required for bacterial clearance in vivo. Nat Med 7: 1209–16, 2001.PubMedCrossRefGoogle Scholar
  49. 49.
    Partida-Sanchez S, Randall TD and Lund FE. Innate immunity is regulated by CD38, an ecto-enzyme with ADP-ribosyl cyclase activity. Microbes Infect 5: 49–58, 2003.PubMedCrossRefGoogle Scholar
  50. 50.
    Perez JF and Sanderson MJ. The frequency of calcium oscillations induced by 5-HT, ACH, and KCl determine the contraction of smooth muscle cells of intrapulmonary bronchioles. J Gen Physiol 125: 535–553, 2005.PubMedCrossRefGoogle Scholar
  51. 51.
    Prakash YS, Kannan MS and Sieck GC. Regulation of intracellular calcium oscillations in porcine tracheal smooth muscle cells. Am J Physiol 272: 966–75, 1997.Google Scholar
  52. 52.
    Prakash YS, Kannan MS, Walseth TF and Sieck GC. Role of cyclic ADP-ribose in the regulation of [Ca2+]i in porcine tracheal smooth muscle. American Journal of Physiology 274: 1653–60, 1998.Google Scholar
  53. 53.
    Riffo-Vasquez Y, Pitchford S and Spina D. Cytokines in airway inflammation. Int J Biochem Cell Biol 32: 833–53, 2000.PubMedCrossRefGoogle Scholar
  54. 54.
    Saxena H, Deshpande DA, Tiegs BC, Yan H, Battafarano RJ, Burrows WM, Damera G, Panettieri RA, DuBose TD, Jr., An SS and Penn RB. The GPCR OGR1 (GPR68) mediates diverse signalling and contraction of airway smooth muscle in response to small reductions in extracellular pH. Br J Pharmacol 166: 981–990, 2012.Google Scholar
  55. 55.
    Sieck GC, White TA, Thompson MA, Pabelick CM, Wylam ME and Prakash YS. Regulation of store-operated Ca2+ entry by CD38 in human airway smooth muscle. Am J Physiol Lung Cell Mol Physiol 294: L378–L385, 2008.PubMedCrossRefGoogle Scholar
  56. 56.
    Tang WX, Chen YF, Zou AP, Campbell WB and Li PL. Role of FKBP12.6 in cADPR-induced activation of reconstituted ryanodine receptors from arterial smooth muscle. Am J Physiol Heart Circ Physiol 282: 1304–10, 2002.Google Scholar
  57. 57.
    Thomas JM, Summerhill RJ, Fruen BR, Churchill GC and Galione A. Calmodulin dissociation mediates desensitization of the cADPR-induced Ca2+ release mechanism. Curr Biol 12: 2018–22, 2002.PubMedCrossRefGoogle Scholar
  58. 58.
    Tirumurugaan KG, Kang BN, Panettieri RA, Foster DN, Walseth TF and Kannan MS. Regulation of the cd38 promoter in human airway smooth muscle cells by TNF-alpha and dexamethasone. Respir Res 9: 26, 2008.PubMedCrossRefGoogle Scholar
  59. 59.
    Tliba O, Deshpande D, Chen H, Van Besien C, Kannan M, Panettieri RA and Amrani Y. IL-13 enhances agonist-evoked calcium signals and contractile responses in airway smooth muscle. Br J Pharmacol 140: 1159–62, 2003.PubMedCrossRefGoogle Scholar
  60. 60.
    Tliba O, Panettieri RA, Jr., Tliba S, Walseth TF and Amrani Y. Tumor necrosis factor-alpha differentially regulates the expression of proinflammatory genes in human airway smooth muscle cells by activation of interferon-beta-dependent CD38 pathway. Mol Pharmacol 66: 322–329, 2004.PubMedCrossRefGoogle Scholar
  61. 61.
    Wang YX, Zheng YM, Mei QB, Wang QS, Collier ML, Fleischer S, Xin HB and Kotlikoff MI. FKBP12.6 and cADPR regulation of Ca2+ release in smooth muscle cells. Am J Physiol Cell Physiol 286: C538–C546, 2004.PubMedCrossRefGoogle Scholar
  62. 62.
    White TA, Johnson S, Walseth TF, Lee HC, Graeff RM, Munshi CB, Prakash YS, Sieck GC and Kannan MS. Subcellular localization of cyclic ADP-ribosyl cyclase and cyclic ADP- ribose hydrolase activities in porcine airway smooth muscle. Biochim Biophys Acta 1498: 64–71, 2000.PubMedCrossRefGoogle Scholar
  63. 63.
    White TA, Kannan MS and Walseth TF. Intracellular calcium signaling through the cADPR pathway is agonist specific in porcine airway smooth muscle. FASEB J 17: 482–4, 2003.PubMedGoogle Scholar
  64. 64.
    Yim PD, Gallos G, Xu D, Zhang Y and Emala CW. Novel expression of a functional glycine receptor chloride channel that attenuates contraction in airway smooth muscle. FASEB J 25: 1706–1717, 2011.PubMedCrossRefGoogle Scholar
  65. 65.
    ZhuGe R, Fogarty KE, Baker SP, McCarron JG, Tuft RA, Lifshitz LM and Walsh JV, Jr. Ca(2+) spark sites in smooth muscle cells are numerous and differ in number of ryanodine receptors, large-conductance K(+) channels, and coupling ratio between them. Am J Physiol Cell Physiol 287: C1577–C1588, 2004.PubMedCrossRefGoogle Scholar
  66. 66.
    ZhuGe R, Fogarty KE, Tuft RA, Lifshitz LM, Sayar K and Walsh JV, Jr. Dynamics of signaling between Ca(2+) sparks and Ca(2+)- activated K(+) channels studied with a novel image-based method for direct intracellular measurement of ryanodine receptor Ca(2+) current. J Gen Physiol 116: 845–864, 2000.PubMedCrossRefGoogle Scholar
  67. 67.
    Zuyderduyn S, Sukkar MB, Fust A, Dhaliwal S and Burgess JK. Treating asthma means treating airway smooth muscle cells. Eur Respir J 32: 265–274, 2008.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  • Deepak A. Deshpande
    • 1
  • Alonso Guedes
    • 2
  • Mythili Dileepan
    • 3
  • Timothy F. Walseth
    • 4
  • Mathur S. Kannan
    • 3
    Email author
  1. 1.Department of Medicine, Pulmonary and Critical Care Medicine, School of MedicineUniversity of MarylandBaltimoreUSA
  2. 2.Department of Anesthesiology, School of Veterinary MedicineUniversity of CaliforniaDavisUSA
  3. 3.Department of Veterinary and Biomedical Sciences, College of Veterinary MedicineUniversity of MinnesotaSt. PaulUSA
  4. 4.Department of PharmacologyUniversity of MinnesotaSt. PaulUSA

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