title: The essential role of protein kinase Cδ in diabetes-induced neural tube defects.
abstract: 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 PKCδ in NTD formation and the underlying mechanisms.
  
  
  METHODS
  PKCδ heterozygous (pkcδ(+/-)) 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 PKCδ homozygous (pkcδ(-/-)) 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/PKCδ(-/-) 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.
  
  
  CONCLUSIONS
  PKCδ plays a critical role in diabetes-induced NTDs, potentially through increasing oxidative and ER stress and JNK-associated stress-response pathways.
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Yuanning
authors.initials: Y
authors.lastname: Cao
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Zhao
authors.forename: Richard L
authors.initials: RL
authors.lastname: Eckert
authors.forename: E Albert
authors.initials: EA
authors.lastname: Reece
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005260:Female; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009436:Neural Tube Defects / Q000209:etiology* / Q000378:metabolism; D018384:Oxidative Stress; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000378:metabolism*; D051745:Protein Kinase C-delta / Q000378:metabolism*; D013311:Streptozocin
chemical_list: D015415:Biomarkers; D013311:Streptozocin; D051745:Protein Kinase C-delta; D048031:JNK Mitogen-Activated Protein Kinases