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Hyperglycemia induces apoptotic signaling in first trimester cytotrophoblast cells (1010.6)
Author(s) -
Leonard Dean,
Horvat Darijana,
Beeram Madhava,
Allen Steven,
Meininger Cynthia,
Zawieja David,
Kuehl Thomas,
Uddin Mohammad
Publication year - 2014
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.28.1_supplement.1010.6
Subject(s) - ctbs , rosiglitazone , phosphorylation , endocrinology , signal transduction , medicine , p38 mitogen activated protein kinases , peroxisome proliferator activated receptor , apoptosis , receptor , txnip , mapk/erk pathway , chemistry , microbiology and biotechnology , biology , oxidative stress , biochemistry , metaplasticity , synaptic plasticity , thioredoxin
Objective : Diabetes mellitus is a risk factor for preeclampsia (preE). The mechanism contributing to this effect is not well known. It is evident that dysfunction of cytotrophoblast cells (CTBs) plays a role in the pathogenesis of preE. We have reported that hyperglycemia downregulates factors for invasion and induces an anti‐angiogenic milieu in CTBs. This study assessed the apoptotic signaling in hyperglycemia‐induced CTBs dysfunction. Methods : Human CTBs were treated with 100, 150, 200, 300 or 400 mg/dL glucose for 48h. Some cells were pretreated with p38 inhibitor (SB203580) or peroxisome proliferator‐activated receptor gamma (PPARγ) ligand (rosiglitazone). Thereafter, cell lysates were utilized to measure Bax, Bcl2, Cox‐2 and PPARγ expression and p38 MAPK phosphorylation by western blot. Comparisons were performed using ANOVA with Duncan’s post hoc test. Results: The expression of Bax (2.5 fold), Bcl2 (1.8 fold), Cox‐2 (2.1 fold) and PPARγ (1.8 fold) and p38 MAPK phosphorylation (1.7 fold) were up‐regulated (p<0.05) in CTBs treated with 蠅150 mg/dL glucose compared to basal (100 mg/dL). SB203580 or rosiglitazone pretreatment attenuated glucose‐induced stress and apoptotic signaling. Conclusions: Exposure of CTBs to hyperglycemia induces apoptotic signaling. Attenuation of this signaling by SB203580 or rosiglitazone pretreatment suggests involvement of p38 and PPARγ in this signaling cascade. Grant Funding Source : N/A