High glucose induces apoptosis in embryonic neural progenitor cells by a pathway involving protein PKC[delta]

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 PKC[delta]-dependent mechanism. Tyrosine phosphorylation of PKC[delta] was required for PKC[delta] 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 PKC[delta]. Moreover, translocation of PKC[delta] and c-Abl complex from the cytoplasm to the nucleus, was blocked by down-regulation of PKC[delta] or c-Abl. Furthermore, we found that interaction of PKC[delta] 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.