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Role of cinobufotalin in the pathogenesis of preeclampsia: in vivo and in vitro studies
Author(s) -
Horvat Darijana,
Kelso Kelsey,
Allen Steven,
Fothergill Russell,
Zawieja David,
Kuehl Thomas,
Uddin Mohammad Nasir
Publication year - 2012
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.26.1_supplement.lb158
Subject(s) - cytotrophoblast , preeclampsia , pathogenesis , apoptosis , in vivo , endocrinology , cell , annexin , medicine , chemistry , andrology , biology , pregnancy , fetus , placenta , biochemistry , genetics , microbiology and biotechnology
Objective Preeclampsia (preE) is a hypertensive disorder of pregnancy. Cardiotonic steroids (CS) are endogenous inhibitors of Na + /K + ATPase. We have shown that one CS, marinobufagenin (MBG), is elevated in preE prior to the development of symptoms. We have also demonstrated that MBG impairs cytotrophoblast (CTB) function, which is critical for placental development. We evaluated the effect of cinobufotalin (CINO), another CS, on pregnant rats and CTB cells to assess its role in preE. Methods Four groups of rats were studied: normal pregnant (NP, n=10) rats, NP injected with MBG (NPM, n=10) rats, NP injected with CINO (NPC, n=10) rats, and a rat model of preE (PDS, n=10). CTB cell function and signaling were assayed after CINO treatment. Results NPC rats showed hypertension and proteinuria similar to PDS and NPM rats. CINO at ≥ 1 nM inhibited CTB cell proliferation, migration, and invasion but had no effect on cell viability. A higher percentage of cells were in the G0/G1 phase in groups treated with ≥ 1 nM CINO. CINO caused an increase in stress signaling p38 MAPK and a positive annexin‐V stain in CTB cells, indicating the activation of apoptotic signaling. However the CINO induced apoptotic signaling was prevented by p38 inhibition. Conclusions We have demonstrated that: 1) CINO induces preE in NP rats and 2) CINO impairs CTB cell function. Therefore, CINO may play a role in the pathogenesis of preE.