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CD38 overexpression influences [Ca 2+ ] i regulation in airway smooth muscle
Author(s) -
Soares Sandra M,
White Thomas A,
Bailey Jeffrey P,
Chini Eduardo N,
Prakash Y S,
Pabelick Christina M,
Sieck Gary C
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1259-a
The importance of the CD38/cyclic adenine diphosphate ribose (cADPR) pathway in intracellular Ca 2+ regulation ([Ca 2+ ] i ) of airway smooth muscle (ASM) is becoming more evident. The bifunctional enzyme CD38, known to regulate cADPR production and degradation, is thought to be key not only for normal airway function, but also in airway hyperreactivity. In this study, we examined [Ca 2+ ] i regulation in human ASM with CD38 overexpression resulting from lipofectamine‐based transfection. RT‐PCR showed increased CD38 mRNA, while fluorescence immunostaining and protein gel electrophoresis revealed increased CD38 expression. ADP ribosyl cyclase activity was greatly enhanced in CD38 transfected cells. Both control and CD38 overexpressing ASM cells were visualized using fura‐2 fluorescence. Basal [Ca 2+ ] i was significantly higher (p<0.05, independent Student's t ‐test) in transfected cells. Furthermore, the peak of the [Ca 2+ ] i response to 1 μM acetylcholine (ACh) was increased with CD38 overexpression. In transfected cells, Ca 2+ influx triggered following depletion of sarcoplasmic reticulum Ca 2+ stores (i.e. store‐operated Ca 2+ entry; SOCE) increased. These results show that CD38 is importantly involved in the regulation of [Ca 2+ ] i in ASM and that overexpression of CD38, as may result from exposure to inflammatory cytokines (e.g., TNF‐a) results in higher basal [Ca 2+ ] i levels and an enhanced [Ca 2+ ] i response to agonist stimulation. Supported by NIH grants GM56686, HL74309, Foundation for Anesthesia Education and Research (FAER)