CD38-cyclic ADP-ribose-mediated calcium signaling in airway myocytes

Deepak A. Deshpande, Alonso Guedes, Mythili Dileepan, Timothy F. Walseth, Mathur S. Kannan

Research output: Chapter in Book/Report/Conference proceedingChapter

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.

Original languageEnglish (US)
Title of host publicationCalcium Signaling In Airway Smooth Muscle Cells
PublisherSpringer International Publishing
Pages247-267
Number of pages21
ISBN (Print)9783319013121, 3319013114, 9783319013114
DOIs
StatePublished - Nov 1 2013

Keywords

  • cADPR
  • CD38
  • Cyclase
  • Cytokine
  • miRNA

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Deshpande, D. A., Guedes, A., Dileepan, M., Walseth, T. F., & Kannan, M. S. (2013). CD38-cyclic ADP-ribose-mediated calcium signaling in airway myocytes. In Calcium Signaling In Airway Smooth Muscle Cells (pp. 247-267). Springer International Publishing. https://doi.org/10.1007/978-3-319-01312-1_13