Role of CD38 in myometrial Ca2+ transients: Modulation by progesterone

Michael Thompson, Hosana Barata Da Silva, Weronika Zielinska, Thomas A. White, Jeffrey P. Bailey, Frances E. Lund, Gary C. Sieck, Eduardo N. Chini

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Oxytocin-induced Ca2+ transients play an important role in myometrial contractions. Here, using a knockout model, we found that the enzyme CD38, responsible for the synthesis of the second messenger cyclic ADP-ribose (cADPR), plays an important role in the oxytocin-induced Ca2+ transients and contraction. We also observed that CD38 is necessary for TNF-α-increased agonist-stimulated Ca2+ transients in human myometrial cells. We provide experimental evidence that the TNF-α effect is mediated by increased expression of the enzyme CD38. First, we observed that TNF-α increased oxytocin-induced Ca2+ transients and CD38 expression in human myometrial cells. Moreover, using small interference RNA technology, we observed that TNF-α stimulation of agonist-induced Ca 2+ transients was abolished by blocking the expression of CD38. In control experiments, we observed that activation of the component of the TNF-α signaling pathway, NF-κB, was not affected by the treatments. Finally, we observed that the effects of TNF-α on CD38 cyclase and oxytocin-induced Ca2+ transients are abolished by progesterone. In conclusion, we provide the first experimental evidence that CD38 is important for myometrial Ca2+ transients and contraction. Moreover, CD38 is necessary for the TNF-α-mediated augmentation of agonist-induced Ca 2+ transients in myometrial cells. We propose that the balance between cytokines and placental steroids regulates the expression of CD38 in vivo and cell responsiveness to oxytocin.

Original languageEnglish (US)
Pages (from-to)E1142-E1148
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume287
Issue number6 50-6
DOIs
StatePublished - Dec 1 2004

Keywords

  • Cyclic adenosine diphosphate-ribose
  • Endoplasmic reticulum
  • Ryanodine channel
  • Small interference ribonucleic acid
  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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