title: AP-2α-dependent regulation of Bcl-2/Bax expression affects apoptosis in the trophoblast.
abstract: Enhanced apoptosis of the cytotrophoblast in early pregnancy is associated with a high risk of preeclampsia. We and others have previously reported that the transcriptional factor, activator protein AP-2α, suppressed trophoblast migration and invasion. However, it is not clear whether AP-2α affects apoptosis in trophoblast cells and whether it regulates expression of apoptosis-related factors Bcl-2 and Bax. We analyzed the expression of AP-2α, Bcl-2 and Bax in placental tissues in severe preeclamptic pregnancies and normotensive pregnancies using immunohistochemistry and real time-PCR. Further, apoptosis was assessed by flow cytometric analysis in the human trophoblastic cell line, BeWo cells, in which AP-2α expression was transiently overexpressed or down-regulated by siRNA. There was significantly higher expression of AP-2α and Bax, but lower expression of Bcl-2 in severe preeclampsia placentas as compared to the control placentas. Overexpression of AP-2α in BeWo cells led to an increased rate of apoptosis, whereas apoptosis was decreased when AP-2α expression was reduced. Furthermore, overexpression of AP-2α increased Bax expression and decreased Bcl-2 expression, whereas down-regulation of AP-2α expression resulted in a decrease in Bax expression and an increase in Bcl-2 expression. AP-2α regulates expression of Bcl-2 and Bax and apoptosis in BeWo cells. These results suggest that AP-2α-mediated regulation of Bcl-2 and Bax regulation influences apoptosis which in turn leads to the pathogenesis of preeclampsia.
authors.affiliation: Department of Clinical Laboratory, The Third Affilicated Hospital of Zhengzhou University, Kangfuqian Street 7, Zhengzhou, 450052, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.forename: Liting
authors.initials: L
authors.lastname: Jia
authors.forename: Shihong
authors.initials: S
authors.lastname: Cui
authors.forename: Ying
authors.initials: Y
authors.lastname: Shi
authors.forename: Aimin
authors.initials: A
authors.lastname: Chang
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.forename: Zhan
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D015153:Blotting, Western; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D011247:Pregnancy; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D050656:Transcription Factor AP-2 / Q000235:genetics / Q000378:metabolism*; D014327:Trophoblasts / Q000166:cytology* / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D050656:Transcription Factor AP-2; D051028:bcl-2-Associated X Protein