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Regulation of store-operated Ca2+ entry by CD38 in human airway smooth muscle.
- Source :
-
American Journal of Physiology: Lung Cellular & Molecular Physiology . Feb2008, Vol. 294, pL378-L385. 8p. 4 Graphs. - Publication Year :
- 2008
-
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+ ([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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10400605
- Volume :
- 294
- Database :
- Academic Search Index
- Journal :
- American Journal of Physiology: Lung Cellular & Molecular Physiology
- Publication Type :
- Academic Journal
- Accession number :
- 30014180
- Full Text :
- https://doi.org/10.1152/ajplung.00394.2007