Calmodulin inhibitor-induced apoptosis was prevented by glycogen synthase kinase-3 inhibitors in PC12 cells

• Published in: Cellular and molecular neurobiology Vol. 27; no. 6; pp. 783 - 790
• Main Authors: Takadera, Tsuneo, Ohyashiki, Takao
• Format: Journal Article
• Language: English
• Published: United States 01.09.2007
• Subjects: Animals; Apoptosis - drug effects; Benzazepines - pharmacology; Calmodulin - antagonists & inhibitors; Caspase 3 - metabolism; Cell Death - drug effects; Glycogen Synthase Kinase 3 - antagonists & inhibitors; Indoles - pharmacology; L-Lactate Dehydrogenase - metabolism; Maleimides - pharmacology; PC12 Cells; Protein Kinase Inhibitors - pharmacology; Rats; Sulfonamides - pharmacology
• ISSN: 0272-4340; 1573-6830
• DOI: 10.1007/s10571-007-9172-y

Calmodulin is known to transduce Ca(2+) signals by interacting with specific target proteins. In order to determine the role of calmodulin in regulating neuronal survival and death, we examined, whether calmodulin inhibitors induce caspase-dependent apoptotic cell death, and whether glycogen synthase kinase-3 is involved in calmodulin inhibitor-induced cell death in PC12 cells. W13, a calmodulin specific inhibitor increased apoptotic cell death with morphological changes characterized by cell shrinkage and nuclear condensation of fragmentation. Glycogen synthase kinase-3 inhibitors prevented calmodulin inhibitor-induced apoptosis. In addition, nerve growth factor and cycloheximide, a protein synthesis inhibitor, completely blocked cell death. Moreover, caspase-3 activation was accompanied by calmodulin inhibitor-induced cell death and inhibited by nerve growth factor. These results suggest that calmodulin inhibitors induce caspase-dependent apoptosis, and the activation of glycogen synthase kinase-3 is involved in the death of PC12 cells.