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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, Shinwon; Ryu, Hye Young; Chung, Kyung Min; Baek, Seung-Hoon; Kim, Eun-Kyoung; Yu, Seong-Woon
- DGIST Authors
- Chung, Kyung Min; Kim, Eun-Kyoung; Yu, Seong-Woon
- Issue Date
- Molecular Brain, 8
- Article Type
- Adult; Animal Cell; Animal Tissue; Apoptosis; Autophagic Cell Death; Autophagosome; Autophagy; Beta Catenin; Caspase 3; Cell Death; Cell Viability; Enzyme Activation; Enzyme Inactivation; Gene Inactivation; Gene Silencing; Glycogen Synthase Kinase-3Beta; Glycogen Synthase Kinase 3Alpha; Hippocampal Neural Stem Cell; Hippocampal Neural Stem Cells; Hippocampus; Insulin; Lipocortin 5; Lysosome; Mammal Cell; Mammalia; Neural Stem Cell; Non-Human; Pharmacological Blocking; Priority Journal; Programmed Cell Death; Protein Expression; Rat; Rattus
- 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
Laboratory of Neuronal Cell Death
Molecular mechanisms of neuronal cell death and neurodegeneration
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