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CINOBUFATALIN IMPAIRS FIRST TRIMESTER CYTOTROPHOBLAST FUNCTIONS VIA CELL CYCLE ARREST AND APOPTOTIC SIGNALING
Author(s) -
Uddin Mohammad Nasir,
Allen Steven R,
Zawieja David C,
Kuehl Thomas J
Publication year - 2011
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.25.1_supplement.lb139
Subject(s) - apoptosis , annexin , cell growth , cell cycle , chemistry , microbiology and biotechnology , cell cycle checkpoint , andrology , cancer research , medicine , biology , biochemistry
Preeclampsia is a hypertensive disorder unique to pregnancy in which marinobufagenin (MBG) is increased. We demonstrated that MBG impairs the cytotrophoblasts (CTB) functions critical for placental development. Cinobufatalin (CBT) is an analog of MBG. The aim of this study is to measure the effect of CBT on CTB cell function. The effect of CBT on CTB cell functions including proliferation, migration and invasion were investigated utilizing first trimester extravillous CTB cells. To elucidate the mechanisms by which CBT impairs CTB function, cell cycle progression and apoptotic signaling were evaluated by FACS analysis of CTBs stimulated with CBT (0.1, 1, 10 and 100 nM). The phosphorylation of p38 was evaluated by ELISA in CTB cells stimulated with CBT (0.1, 1, 10 and 100 nM). Apoptosis was evaluated by annexin‐V staining. CBT ≥1.0 nM significantly inhibited CTB cell proliferation (80%), migration (70%) and invasion (60%), whereas 0.1 nM CBT had no effect. There was a significantly higher percentage (80%) of cells in the G0/G1 phase in the cells treated with ≥1.0 nM CBT compared to basal and to 0.1 nM treated cells (55%). CBT stimulated a significant increase in dead cells by apoptotic bleb assay, increased the activation of p38 and a positive annexin‐V staining indicating the activation of apoptosis. CBT‐induced impairment of CTB cell function occurs via cell cycle arrest, p38 activation, and the activation of apoptosis.