RRC ID 18714
Author Takadera T, Ohtsuka M, Aoki H.
Title Chelation of extracellular calcium-induced cell death was prevented by glycogen synthase kinase-3 inhibitors in PC12 cells.
Journal Cell Mol Neurobiol
Abstract Calcium ion is a secondary messenger that mediates a variety of physiological responses of neurons, including cell survival responses. To determine the role of calcium in regulating neuronal survival and death, we examined whether chelation of extracellular calcium with EGTA induces caspase-dependent apoptotic cell death and whether glycogen synthase kinase-3 is involved in EGTA-induced cell death in PC12 cells. EGTA increased apoptotic cell death with morphological changes characterized by cell shrinkage and nuclear condensation and fragmentation accompanied by caspase activation. EGTA increased GRP78 protein expression, suggesting that EGTA induces ER stress. Glycogen synthase kinase-3 inhibitors prevented EGTA-induced apoptosis. In addition, nerve growth factor and insulin growth factor-I completely blocked EGTA-induced cell death. Moreover, caspase-3 activation was inhibited by glycogen synthase kinase-3 inhibitors. These results suggest that chelation of extracellular calcium with EGTA induces caspase-dependent apoptosis, and the activation of glycogen synthase kinase-3 is involved in the death of PC12 cells.
Volume 30(2)
Pages 193-8
Published 2010-3-1
DOI 10.1007/s10571-009-9442-y
PMID 19688259
MeSH Animals Apoptosis / physiology Benzazepines / metabolism Calcium* / metabolism Calcium* / pharmacology Caspases / metabolism Cell Death / drug effects* Chelating Agents / metabolism* Egtazic Acid / metabolism Enzyme Activation Glycogen Synthase Kinase 3 / antagonists & inhibitors* Heat-Shock Proteins / metabolism Indoles / metabolism Insulin-Like Growth Factor I / metabolism Maleimides / metabolism Nerve Growth Factor / metabolism PC12 Cells Rats
IF 3.606
Times Cited 6
Human and Animal Cells PC-12(RCB0009)