Altered protein kinase C activation associated with rat embryonic dysmorphogenesis.
It has been suggested that protein kinase C (PKC) is involved in the etiology of diabetic complications. The aim of the present study was to investigate the putative involvement of different PKC isoforms (alpha, beta1, beta 2, gamma, delta, epsilon, and zeta) in the embryopathy of diabetic rat pregnancy. Embryos were collected from normal and diabetic rats and assayed for PKC activity, PKC mRNA levels, and PKC protein distribution on gestational d 10 and 11. Embryos of diabetic rats showed markers of increased activity of PKC-alpha, PKC-beta1, PKC-gamma, PKC-delta, and PKC-zeta compared with embryos of normal rats on d 10. In addition, the malformed embryos had further increased PKC-gamma, and PKC-delta activity markers compared with nonmalformed embryos of diabetic rats on gestational d 10. In contrast, maternal diabetes caused only two alterations in PKC activity markers on gestational d 11, i.e. both PKC-alpha and PKC-zeta were decreased in embryos of diabetic rats. We found increased mRNA levels of PKC-beta 1 and PKC-zeta on d 10 in embryos of diabetic rats and decreased mRNA levels of PKC-gamma on d 11 in embryos of diabetic rats. Malformed embryos from diabetic rats showed increased distribution of PKC-beta 1 and PKC-beta 2 protein in the tissue compared with nonmalformed embryos from diabetic rats and embryos from normal rats. We conclude that diabetic rat embryopathy may be associated with increased activity and enhanced tissue distribution of several PKC isoforms in early organogenesis.
Gäreskog
Mattias
M
Department of Medical Cell Biology, Uppsala University, Biomedical Center, P.O. Box 571, SE-751 23 Uppsala, Sweden. Mattias.Gareskog@medcellbiol.uu.se
Wentzel
Parri
P
D000015:Abnormalities, Multiple / Q000378:metabolism*; D000818:Animals; D048909:Diabetes Complications / Q000378:metabolism*; D016640:Diabetes, Gestational / Q000378:metabolism*; D005260:Female; D005317:Fetal Growth Retardation / Q000378:metabolism*; D005865:Gestational Age; D011247:Pregnancy; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha; D051745:Protein Kinase C-delta; D051744:Protein Kinase C-epsilon; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D000099221:Protein Kinase C zeta
D011493:Protein Kinase C; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha; D051745:Protein Kinase C-delta; D051744:Protein Kinase C-epsilon; D012333:RNA, Messenger; D000099221:Protein Kinase C zeta; C497260:Prkcd protein, rat; C497257:Prkce protein, rat; C087857:protein kinase C gamma