TY - JOUR
T1 - Role of CD38 in myometrial Ca2+ transients
T2 - Modulation by progesterone
AU - Thompson, Michael
AU - Da Silva, Hosana Barata
AU - Zielinska, Weronika
AU - White, Thomas A.
AU - Bailey, Jeffrey P.
AU - Lund, Frances E.
AU - Sieck, Gary C.
AU - Chini, Eduardo N.
PY - 2004/12
Y1 - 2004/12
N2 - 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.
AB - 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.
KW - Cyclic adenosine diphosphate-ribose
KW - Endoplasmic reticulum
KW - Ryanodine channel
KW - Small interference ribonucleic acid
KW - Tumor necrosis factor-α
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U2 - 10.1152/ajpendo.00122.2004
DO - 10.1152/ajpendo.00122.2004
M3 - Article
C2 - 15339743
AN - SCOPUS:8544257056
SN - 0193-1849
VL - 287
SP - E1142-E1148
JO - American Journal of Physiology - Endocrinology and Metabolism
JF - American Journal of Physiology - Endocrinology and Metabolism
IS - 6 50-6
ER -