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

Gary C Sieck, Thomas A. White, Michael A. Thompson, Christina M Pabelick, Mark Wylam, Y.s. Prakash

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

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+ ([Ca 2+]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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume294
Issue number2
DOIs
StatePublished - Feb 2008

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Small Interfering RNA
Smooth Muscle Myocytes
Smooth Muscle
ADP-ribosyl Cyclase
Cyclic ADP-Ribose
Sarcoplasmic Reticulum
Transfection
Cytokines

Keywords

  • ADP ribosyl cyclase
  • Bronchial smooth muscle
  • Cyclic ADP ribose
  • Sarcoplasmic reticulum
  • Small interfering RNA
  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Cell Biology
  • Physiology

Cite this

Regulation of store-operated Ca2+ entry by CD38 in human airway smooth muscle. / Sieck, Gary C; White, Thomas A.; Thompson, Michael A.; Pabelick, Christina M; Wylam, Mark; Prakash, Y.s.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 294, No. 2, 02.2008.

Research output: Contribution to journalArticle

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