Altered protein kinase C activation associated with rat embryonic dysmorphogenesis

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.