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Demonstration of the Essential Role of Protein Kinase C Isoforms in Hyperglycemia-Induced Embryonic Malformations

Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, Maryland, zzhao{at}upi.umaryland.edu

Ying-King Wu, MD

Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, Maryland

E. Albert Reece, MD, PhD, MBA

Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, Maryland

To address the role of PKC isoforms in hyperglycemia-induced apoptosis and malformations in the embryos of diabetic pregnancies, expression of PKC, β1, β 2, , , , and was examined in the neural tube of rat embryos and showed to overlap with the regions of increased apoptosis. Levels of activated (phosphorylated) PKC , β2, and were increased in the embryos of diabetic dams whereas those of PKC and were decreased when compared with those in control groups. Cytosolic phospholipase A₂ (cPLA₂) was also activated. Blocking the activity of PKC , β2, and using isoform-specific inhibitors in embryos cultured in hyperglycemia (40 mM) reduced malformation rates when compared with those in untreated hyperglycemic and euglycemic (8.3 mM) groups. These observations demonstrate that PKC, β2, and play an essential role in diabetic embryopathy. Activation of cPLA₂ was also decreased, suggesting that PKCs mediate the hyperglycemic effects through the cPLA₂-phospholipid peroxidation pathway.

Key Words: Diabetic embryopathy • apoptosis • PKC • cPLA2.

Reproductive Sciences, Vol. 15, No. 4, 349-356 (2008)
DOI: 10.1177/1933719108316986


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