title: High glucose induces apoptosis in embryonic neural progenitor cells by a pathway involving protein PKCδ.
abstract: Diabetic-induced neural tube defects in embryos are caused by apoptosis of neural progenitor cells (NPCs); however, the underlying mechanisms are poorly understood. The present study is aimed to investigate the specific cellular proteins that may be involved in apoptosis of NPCs. We show here that hyperglycemia-induced apoptosis of NPCs was through a PKCδ-dependent mechanism. Tyrosine phosphorylation of PKCδ was required for PKCδ binding to c-Abl in the cytoplasm, and inhibition of c-Abl by STI571 or knock-down of c-Abl by RNAi decreased the phosphorylation of PKCδ. Moreover, translocation of PKCδ and c-Abl complex from the cytoplasm to the nucleus, was blocked by down-regulation of PKCδ or c-Abl. Furthermore, we found that interaction of PKCδ and c-Abl played a crucial role in p53 accumulation in the nucleus, which was linked to the apoptosis of NPCs in response to high glucose.
authors: Department of Histology and Embryology, Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong, 250012, PR China.
authors: Shangming
authors: S
authors: Liu
authors: Qiuhuan
authors: Q
authors: Yuan
authors: Shidou
authors: S
authors: Zhao
authors: Jingjing
authors: J
authors: Wang
authors: Yuji
authors: Y
authors: Guo
authors: Fuwu
authors: F
authors: Wang
authors: Yanmin
authors: Y
authors: Zhang
authors: Qian
authors: Q
authors: Liu
authors: Shuai
authors: S
authors: Zhang
authors: Eng-Ang
authors: EA
authors: Ling
authors: Aijun
authors: A
authors: Hao
mesh_terms: D000818:Animals; D017209:Apoptosis; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D005260:Female; D005947:Glucose / Q000494:pharmacology*; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D010766:Phosphorylation; D051745:Protein Kinase C-delta / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016315:Proto-Oncogene Proteins c-abl / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53; D016315:Proto-Oncogene Proteins c-abl; D051745:Protein Kinase C-delta; D005947:Glucose