Cited 10 time in webofscience Cited 11 time in scopus

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

Title
Regulation of autophagic cell death by glycogen synthase kinase-3 beta in adult hippocampal neural stem cells following insulin withdrawal
Authors
Ha, S[Ha, Shinwon]Ryu, HY[Ryu, Hye Young]Chung, KM[Chung, Kyung Min]Baek, SH[Baek, Seung-Hoon]Kim, EK[Kim, Eun-Kyoung]Yu, SW[Yu, Seong-Woon]
DGIST Authors
Ha, S[Ha, Shinwon]; Ryu, HY[Ryu, Hye Young]; Chung, KM[Chung, Kyung Min]; Kim, EK[Kim, Eun-Kyoung]Yu, SW[Yu, Seong-Woon]
Issue Date
2015-05-19
Citation
Molecular Brain, 8
Type
Article
Article Type
Article
Keywords
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
ISSN
1756-6606
Abstract
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.
URI
http://hdl.handle.net/20.500.11750/2898
DOI
10.1186/s13041-015-0119-9
Publisher
BioMed Central Ltd.
Related Researcher
Files:
There are no files associated with this item.
Collection:
Core Protein Resources Center1. Journal Articles
Brain and Cognitive SciencesLab of Neuro-Metabolism & Neurometabolomic Research Center1. Journal Articles


qrcode mendeley

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE