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Improving the redox potential of gestational diabetic endothelial cells: protective actions of sulforaphane
Author(s) -
Patel Bijal,
Siow Richard CM,
Mann Giovanni E.
Publication year - 2013
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.27.1_supplement.1187.14
Subject(s) - sulforaphane , oxidative stress , gestational diabetes , downregulation and upregulation , umbilical vein , endocrinology , medicine , fetus , antioxidant , heme oxygenase , chemistry , biology , heme , gestation , pregnancy , biochemistry , enzyme , gene , in vitro , genetics
Rationale Gestational diabetes mellitus (GDM) is characterized by hyperglycemia and/or impaired glucose tolerance and affects 2–7% of pregnancies. In utero exposure to enhanced oxidative stress increases the risk of type 2 diabetes and cardiovascular disease in offspring due to fetal programming. We have previously shown that GDM impairs nuclear factor erythroid 2‐related factor 2 (Nrf2) mediated upregulation of heme oxygenase‐1 (HO‐1) and NAD(P)H: quinone oxidoreductase 1 (NQO1) expression in fetal umbilical vein endothelial cells (HUVEC). Methods and Results In the present study, we examined whether SFN, a known electrophilic inducer of Nrf2, modulates antioxidant stress protein expression differentially in HUVEC from normal and GDM pregnancies. Cells were treated with SFN (2.5μM) for 0–24h, immunoblotted for HO‐1, NQO1 and Nrf2 and mRNA levels determined by qRT‐PCR. NQO1 activity was determined using the Prochaska assay. Immunfluorescence was employed to study nuclear translocation of Nrf2. Basal levels of HO‐1 and NQO1 mRNA and protein expression were significantly lower in GDM ( p <0.05), however SFN significantly ( p <0.05) upregulated mRNA (HO‐1 by ~5‐fold, NQO1 by ~2‐fold) and protein (12h and 24h) levels and increased NQO1 activity. Conclusions Our findings suggest that impaired antioxidant defences in cells derived from GDM pregnancies, may be restored by SFN. We hypothesize that SFN may potentially maintain antioxidant defences and thereby delay the onset and consequences of GDM. Supported by British Heart Foundation