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Regulation of autophagic cell death by glycogen synthase kinase-3 beta in adult hippocampal neural stem cells following insulin withdrawal

Regulation of autophagic cell death by glycogen synthase kinase-3 beta in adult hippocampal neural stem cells following insulin withdrawal
Ha, ShinwonRyu, Hye YoungChung, Kyung MinBaek, Seung-HoonKim, Eun-KyoungYu, Seong-Woon
DGIST Authors
Chung, Kyung Min; Kim, Eun-KyoungYu, Seong-Woon
Issue Date
Molecular Brain, 8
Article Type
AdultAnimal CellAnimal TissueApoptosisAutophagic Cell DeathAutophagosomeAutophagyBeta CateninCaspase 3Cell DeathCell ViabilityEnzyme ActivationEnzyme InactivationGene InactivationGene SilencingGlycogen Synthase Kinase-3BetaGlycogen Synthase Kinase 3AlphaHippocampal Neural Stem CellHippocampal Neural Stem CellsHippocampusInsulinLipocortin 5LysosomeMammal CellMammaliaNeural Stem CellNon-HumanPharmacological BlockingPriority JournalProgrammed Cell DeathProtein ExpressionRatRattus
Background: Neural stem cells (NSCs) hold great potential for the treatment of neurodegenerative diseases. However, programmed cell death (PCD) provoked by the harsh conditions evident in the diseased brain greatly undermines the potential of NSCs. Currently, the mechanisms of PCD that effect NSCs remain largely unknown. Results: We have previously reported that hippocampal neural stem (HCN) cells derived from the adult rat brain undergo autopahgic cell death (ACD) following insulin withdrawal without hallmarks of apoptosis despite their normal apoptotic capabilities. In this study, we demonstrate that glycogen synthase kinase 3β (GSK-3β) induces ACD in insulin-deprived HCN cells. Both pharmacological and genetic inactivation of GSK-3β significantly decreased ACD, while activation of GSK-3β increased autophagic flux and caused more cell death without inducing apoptosis following insulin withdrawal. In contrast, knockdown of GSK-3α barely affected ACD, lending further support to the critical role of GSK-3β. Conclusion: Collectively, these data demonstrate that GSK-3β is a key regulator of ACD in HCN cells following insulin withdrawal. The absence of apoptotic indices in GSK-3β-induced cell death in insulin-deprived HCN cells corroborates the notion that HCN cell death following insulin withdrawal represents the genuine model of ACD in apoptosis-intact mammalian cells and identifies GSK-3β as a key negative effector of NSC survival downstream of insulin signaling. © 2015 Ha et al.; licensee BioMed Central.
BioMed Central Ltd.
Related Researcher
  • Author Yu, Seong-Woon Laboratory of Neuronal Cell Death
  • Research Interests Molecular mechanisms of neuronal cell death and neurodegeneration
ETC1. Journal Articles
Department of Brain and Cognitive SciencesLab of Neuro-Metabolism & Neurometabolomic Research Center1. Journal Articles
Department of Brain and Cognitive SciencesLaboratory of Neuronal Cell Death1. Journal Articles

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