The essential role of protein kinase Cδ in diabetes-induced neural tube defects

Background: Maternal diabetes causes neural tube defects (NTDs) in the embryos via activating protein kinase Cs (PKCs), which regulate programmed cell death (apoptosis). The aims of this study are to investigate the role of proapoptotic PKC delta in NTD formation and the underlying mechanisms. Methods: PKC delta heterozygous (pkc delta(+/-)) female mice were diabetic (DM) induced by intravenous injection of streptozotocin. Occurrence of NTDs was evaluated at embryonic day 11.5 and compared between wild type (WT) and PKC delta homozygous (pkc delta(-/-)) embryos. Changes in oxidative and endoplasmic reticulum (ER) stress-associated factors and stress-response c-Jun N-terminal kinases (JNKs) were assessed using Western blot assay. Results: Compared to DM/WT, the DM/PKC delta(-/-) embryos had significantly lower NTD rate and lower levels of oxidative and ER stress factors and JNK activation. These values were similar to those in the non-diabetic control group. Conclusion: PKC delta plays a critical role in diabetes-induced NTDs, potentially through increasing oxidative and ER stress and JNK-associated stress-response pathways.