Possible involvement of PKC isoforms in signalling placental apoptosis in intrauterine growth retardation.
Apoptosis contributes to uteroplacental dsyfunction in intrauterine growth retardation (IUGR). Specific protein kinase C (PKC) isoforms regulate apoptosis in other cell types. PKC isoforms thought to be anti-apoptotic include the conventional PKC isoforms (cPKC-alpha, -beta I and -beta II), whereas the novel PKC isoforms nPKC-delta and nPKC-epsilon may be apoptotic. Dexamethasone administration during the last third of pregnancy in the rat leads to IUGR. We used the dexamethasone model to test the hypothesis that adverse changes in fetal growth might be associated with a modified placental PKC isoform profile. Dexamethasone administered from day 15 of gestation via subcutaneous infusion (osmotic minipump; 100 or 200 microg dexamethasone/kg maternal body wt. per day) induced a dose-dependent decline in placental and fetal body weights at day 21 of gestation. Placental protein expression of all three cPKC isoforms was downregulated by maternal dexamethasone exposure, whereas placental nPKC-epsilon protein expression and activity was significantly upregulated in a dose-dependent manner. These data indicate that IUGR induced by excessive glucocorticoid exposure late in pregnancy leads to changes in the placental PKC isoform profile consistent with the concept that members of the PKC family participate in apoptosis signalling in the placenta.
Sugden
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MC
Department of Diabetes and Metabolic Medicine, Division of General and Developmental Medicine, St. Bartholomew's and the Royal London School of Medicine and Dentistry, Queen Mary, University of London, London E1 4NS, UK. m.c.sugden@qmw.ac.uk
Langdown
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ML
D000818:Animals; D017209:Apoptosis; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005317:Fetal Growth Retardation / Q000209:etiology*; D005938:Glucocorticoids / Q000008:administration & dosage / Q000009:adverse effects; D007527:Isoenzymes / Q000502:physiology; D010920:Placenta / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D010922:Placenta Diseases / Q000201:enzymology / Q000473:pathology; D011247:Pregnancy; D011493:Protein Kinase C / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction
D005938:Glucocorticoids; D007527:Isoenzymes; D003907:Dexamethasone; D011493:Protein Kinase C