Expression, Regulation, and Function of the Calmodulin Accessory Protein PCP4/PEP-19 in Myometrium. (December 2019)

• Record Type: Journal Article
• Authors: He, Lily; Lee, Gene T.; Zhou, Helen; Buhimschi, Irina A.; Buhimschi, Catalin S.; Weiner, Carl P.; Mason, Clifford W.
• Is Part Of: Reproductive sciences. Volume 26:Number 12(2019:Dec.)
• Page Start: 1650
• Page End: 1660
• Publication Date: 2019-12
• Subjects: calcium -- calmodulin -- myometrium -- Purkinje cell protein-4; Reproductive health -- Periodicals; Reproduction -- Periodicals; 612.6
• DOI: 10.1177/1933719119828072
• Languages: English
• ISSNs: 1933-7191

Abstract

Objective: Calmodulin (CaM) plays a key role in the orchestration of Ca 2+ signaling events, and its regulation is considered an important component of cellular homeostasis. The control of uterine smooth muscle function is largely dependent on the regulation of Ca 2+ and CaM signaling. The objective of this study was to investigate the expression, function, and regulation of CaM regulatory proteins in myometrium during pregnancy. Study Design: Myometrium was obtained from nonpregnant women and 4 groups of pregnant women at the time their primary cesarean delivery: (i) preterm not in labor, (ii) preterm in labor with clinical and/or histological diagnosis of chorioamnionitis, (3) term not in labor; and (4) term in labor. The effect of perinatal inflammation on pcp4/pep-19 expression was evaluated in a mouse model of Ureaplasma parvum- induced chorioamnionitis. Human myometrial cells stably expressing wild-type and mutant forms of PCP4/PEP-19 were used in the evaluation of agonist-induced intracellular Ca 2+ mobilization. Results: Compared to other CaM regulatory proteins, PCP4/PEP-19 transcripts were more abundant in human myometrium. The expression of PCP4/PEP-19 was lowest in myometrium of women with preterm pregnancy and chorioamnionitis. In the mouse uterus, pcp4/pep-19 expression was lower in late compared to mid-gestation and decreased in mice injected intra-amniotic with Ureaplasma parvum. In myometrial smooth muscle cells, tumor necrosis factor alpha and progesterone decreased and PCP4/PEP-19 promoter activity increased. Finally, the overexpression of PCP4/PEP-19 reduced agonist-induced intracellular Ca 2+ levels in myometrial cells. Conclusion: The decreased expression of PCP4/PEP-19 in myometrium contributes to a loss of quiescence in response to infection-induced inflammation at preterm pregnancy.