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Marinobufagenin is an upstream modulator of Gadd45a stress signaling in cytotrophoblast cells
Author(s) -
Uddin Mohammad Nasir,
Horvat Darijana,
DeMorrow Sharon,
Agunanne Enoch,
Puschett Jules B
Publication year - 2010
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.24.1_supplement.703.10
Subject(s) - downregulation and upregulation , microbiology and biotechnology , phosphorylation , chemistry , oxidative stress , cell cycle checkpoint , signal transduction , p38 mitogen activated protein kinases , cytotrophoblast , cell cycle , cell , biology , mapk/erk pathway , biochemistry , fetus , placenta , pregnancy , genetics , gene
Objective Marinobufagenin (MBG), a cardiotonic steroid, is increased in preeclampsia (PE). Gadd45a is involved in the pathophysiological changes observed in PE. Cytotrophoblast (CTB) cells play an important role in placental development. Study aim to elucidate the role of MBG in Gadd45a signaling in CTB cells. Methods CTB cells were treated with various concentrations of MBG (0, 0.1, 1, 10 or 100 nM). Gadd45a expression and p38 phosphorylation were measured by immunoblotting. The degree of cell cycle arrest was determined by FACS analysis. sFlt‐1 and 8‐isoprostane were measured by EIA. Gadd45a expression was inhibited in CTB cells via siRNA‐mediated knock down. Results Gadd45a expression and p38 phosphorylation were significantly upregulated in the 1, 10 and 100 nM MBG‐treated cells compared to vehicle‐treated cells. 0.1 nM MBG 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 MBG compared to basal and to 0.1 nM treated cells (55%). The application of MBG ≥1 nM significantly increased the secretion of sFlt‐1 and 8‐isoprostane. The RNAi‐mediated inhibition of Gadd45a attenuated MBG‐induced CTB cell stress signaling. Conclusions MBG caused upregulation of p38 phosphorylation and cell cycle arrest, and increased the secretion of sFlt‐1 and 8‐isoprostane. These alterations occurred as a result of Gadd45a stress signaling.