Altered protein kinase C activation associated with rat embryonic dysmorphogenesis

Mattias Gäreskog1, Parri Wentzel

  • 1Department of Medical Cell Biology, Uppsala University, Biomedical Center, P.O. Box 571, SE-751 23 Uppsala, Sweden. Mattias.Gareskog@medcellbiol.uu.se

Pediatric Research
|October 22, 2004
PubMed

Insights

Diabetic embryopathy in rats is linked to altered protein kinase C (PKC) activity and distribution. Specific PKC isoforms show increased activity and tissue presence in embryos from diabetic mothers, particularly during early organogenesis.

Area of Science:

  • Biochemistry
  • Developmental Biology
  • Endocrinology

Background:

  • Protein kinase C (PKC) involvement in diabetic complications is suggested.
  • Diabetic embryopathy is a known complication of poorly controlled diabetes during pregnancy.

Purpose of the Study:

  • To investigate the role of various protein kinase C (PKC) isoforms (alpha, beta1, beta2, gamma, delta, epsilon, zeta) in diabetic rat embryopathy.
  • To assess PKC activity, mRNA levels, and protein distribution in embryos from diabetic and normal pregnancies.

Main Methods:

  • Embryos were collected from normal and diabetic rats on gestational days 10 and 11.
  • Assays for PKC activity, PKC mRNA levels, and PKC protein distribution were performed.
  • Comparison between embryos from diabetic vs. normal rats, and malformed vs. non-malformed embryos from diabetic rats.

Main Results:

  • Increased activity of PKC-alpha, -beta1, -gamma, -delta, and -zeta was observed in embryos from diabetic rats on day 10.
  • Malformed embryos showed further increased PKC-gamma and -delta activity.
  • Increased mRNA levels of PKC-beta1 and -zeta on day 10, and decreased PKC-gamma mRNA on day 11 were noted.
  • Enhanced tissue distribution of PKC-beta1 and -beta2 protein was found in malformed embryos.

Conclusions:

  • Diabetic rat embryopathy is associated with altered activity of multiple PKC isoforms during early organogenesis.
  • Increased activity and tissue distribution of specific PKC isoforms may contribute to the development of diabetic embryopathy.

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