caa a22 4500 606234578 CHVBK 20210128101238.0 cr unu---uuuuu 210128e20150701xx s 000 0 eng 10.1007/s11010-015-2398-y doi (NATIONALLICENCE)springer-10.1007/s11010-015-2398-y Hyperglycemia down-regulates cGMP-dependent protein kinase I expression in first trimester cytotrophoblast cells [Elektronische Daten] [Tammy Nguyen, Saunders Lin, Ahmed Pantho, Belinda Kohl-Thomas, Madhava Beeram, David Zawieja, Thomas Kuehl, M. Uddin] 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 945mg/dL glucose for 48h. Some cells were pretreated with a p38 inhibitor (10μM SB203580) or 10μM 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 >135mg/dL glucose compared to basal (45mg/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. Springer Science+Business Media New York, 2015 Cytotrophoblast cells nationallicence Hyperglycemia nationallicence Pregnancy nationallicence Microvascular complications nationallicence Preeclampsia nationallicence Nguyen Tammy Texas A&M College of Medicine, Temple, TX, USA aut Lin Saunders Texas A&M College of Medicine, Temple, TX, USA aut Pantho Ahmed University of Texas, Austin, TX, USA aut Kohl-Thomas Belinda Department of Obstetrics & Gynecology, Baylor Scott & White Healthcare/Texas A&M Health Science Center College of Medicine, Temple, TX, USA aut Beeram Madhava Texas A&M College of Medicine, Temple, TX, USA aut Zawieja David Texas A&M College of Medicine, Temple, TX, USA aut Kuehl Thomas Texas A&M College of Medicine, Temple, TX, USA aut Uddin M. Texas A&M College of Medicine, Temple, TX, USA aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 405/1-2(2015-07-01), 81-88 0300-8177 405:1-2<81 2015 405 11010 https://doi.org/10.1007/s11010-015-2398-y text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2398-y text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Nguyen Tammy Texas A&M College of Medicine, Temple, TX, USA aut NATIONALLICENCE 700 1- Lin Saunders Texas A&M College of Medicine, Temple, TX, USA aut NATIONALLICENCE 700 1- Pantho Ahmed University of Texas, Austin, TX, USA aut NATIONALLICENCE 700 1- Kohl-Thomas Belinda Department of Obstetrics & Gynecology, Baylor Scott & White Healthcare/Texas A&M Health Science Center College of Medicine, Temple, TX, USA aut NATIONALLICENCE 700 1- Beeram Madhava Texas A&M College of Medicine, Temple, TX, USA aut NATIONALLICENCE 700 1- Zawieja David Texas A&M College of Medicine, Temple, TX, USA aut NATIONALLICENCE 700 1- Kuehl Thomas Texas A&M College of Medicine, Temple, TX, USA aut NATIONALLICENCE 700 1- Uddin M. Texas A&M College of Medicine, Temple, TX, USA aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 405/1-2(2015-07-01), 81-88 0300-8177 405:1-2<81 2015 405 11010