NDLI: Hyperglycemia down-regulates cGMP-dependent protein kinase I expression in first trimester cytotrophoblast cells

Content Provider	Springer Nature Link
Author	Nguyen, Tammy Lin, Saunders Pantho, Ahmed F. Kohl Thomas, Belinda M. Beeram, Madhava R. Zawieja, David C. Kuehl, Thomas J. Uddin, M. Nasir
Copyright Year	2015
Abstract	Diabetes in pregnancy is associated with microvascular complications and a higher incidence of preeclampsia. The regulatory signaling pathways involving nitric oxide, cGMP, and cGMP-dependent protein kinase (PKG) have been shown to be down-regulated under diabetic conditions and contribute to the pathogenesis of vascular complications in diabetes. The present study was undertaken to investigate how high glucose concentrations regulate PKG expression in cytotrophoblast cells (CTBs). Human CTBs (Sw. 71) were treated with 45, 135, 225, 495, or 945 mg/dL glucose for 48 h. Some cells were pretreated with a p38 inhibitor (10 μM SB203580) or 10 μM rosiglitazone. After treatment, the cell lysates were subjected to measure the expression of protein kinase G1α (PKG1α), protein kinase G1β (PKG1β), soluble guanylate cyclase 1α (sGC1α), and soluble guanylate cyclase 1 β (sGC1β) by Western blot. Statistical comparisons were performed using analysis of variance with Duncan’s post hoc test. The expressions of PKG1α, PKG1β, sGC1α, and sGC1β were significantly down-regulated (p < 0.05) in CTBs treated with >135 mg/dL glucose compared to basal (45 mg/dL). The hyperglycemia-induced down-regulation of cGMP and cGMP-dependent PKG were attenuated by the SB203580 or rosiglitazone pretreatment. Exposure of CTBs to excess glucose down-regulates cGMP and cGMP-dependent PKG, contributing to the development of vascular complications in diabetic mothers during pregnancy. The attenuation of hyperglycemia-induced down-regulation of PKG proteins by SB203580 or rosiglitazone pretreatment further suggests the involvement of stress signaling mechanisms in this process.
Starting Page	81
Ending Page	88
Page Count	8
File Format	PDF
ISSN	03008177
Journal	Molecular and Cellular Biochemistry
Volume Number	405
Issue Number	1-2
e-ISSN	15734919
Language	English
Publisher	Springer US
Publisher Date	2015-04-12
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Cytotrophoblast cells Hyperglycemia Pregnancy Microvascular complications Preeclampsia Biochemistry Medical Biochemistry Oncology Cardiology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Medicine Clinical Biochemistry Molecular Biology

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