Ketamine-induced apoptosis in cultured rat cortical neurons.
Recent data suggest that anesthetic drugs cause neurodegeneration during development. Ketamine is frequently used in infants and toddlers for elective surgeries. The purpose of this study is to determine whether glycogen synthase kinase-3 (GSK-3) is involved in ketamine-induced apoptosis. Ketamine increased apoptotic cell death with morphological changes which were characterized by cell shrinkage, nuclear condensation or fragmentation. In addition, insulin growth factor-1 completely blocked the ketamine-induced apoptotic cell death. Ketamine decreased Akt phosphorylation. GSK-3 is known as a downstream target of Akt. The selective inhibitors of GSK-3 prevented the ketamine-induced apoptosis. Moreover, caspase-3 activation was accompanied by the ketamine-induced cell death and inhibited by the GSK-3 inhibitors. These results suggest that activation of GSK-3 is involved in ketamine-induced apoptosis in rat cortical neurons.
Takadera
Tsuneo
T
Department of Clinical Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa 920-1148, Japan. t-takadera@hokuriku-u.ac.jp
Ishida
Akira
A
Ohyashiki
Takao
T
D000778:Anesthetics, Dissociative / Q000009:adverse effects*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects* / Q000196:embryology / Q000201:enzymology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D007649:Ketamine / Q000009:adverse effects*; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D000778:Anesthetics, Dissociative; D016202:N-Methylaspartate; D007649:Ketamine; D016291:Dizocilpine Maleate; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases