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Mediation of Autophagic Cell Death by Type 3 Ryanodine Receptor (RyR3) in Adult Hippocampal Neural Stem Cells

Title
Mediation of Autophagic Cell Death by Type 3 Ryanodine Receptor (RyR3) in Adult Hippocampal Neural Stem Cells
Authors
Chung, KM[Chung, Kyung Min]Jeong, EJ[Jeong, Eun-Ji]Park, H[Park, Hyunhee]An, HK[An, Hyun-Kyu]Yu, SW[Yu, Seong-Woon]
DGIST Authors
Chung, KM[Chung, Kyung Min]; Jeong, EJ[Jeong, Eun-Ji]; Park, H[Park, Hyunhee]; An, HK[An, Hyun-Kyu]; Yu, SW[Yu, Seong-Woon]
Issue Date
2016-05-06
Citation
Frontiers in Cellular Neuroscience, 10
Type
Article
Article Type
Article
Keywords
AdultAnimal CellAnimal ExperimentAnimal ModelAutophagic Cell DeathAutophagyCaffeineCalcium TransportCaspase 9Cell DeathConfocal MicroscopyControlled StudyDantroleneER Ca2+Fluorescence MicroscopyImmunofluorescenceInsulinInsulin WithdrawalIP3 ReceptorsMaleNeural Stem CellNon-HumanProgrammed Cell DeathProtein ExpressionRatReal Time Polymerase Chain ReactionRyanodine Receptor 3Ryanodine ReceptorsStaurosporineTime Lapse ImagingUpregulationWestern Blotting
ISSN
1662-5102
Abstract
Cytoplasmic Ca2+ actively engages in diverse intracellular processes from protein synthesis, folding and trafficking to cell survival and death. Dysregulation of intracellular Ca2+levels is observed in various neuropathological states including Alzheimer’s and Parkinson’s diseases. Ryanodine receptors (RyRs) and inositol 1,4,5-triphosphate receptors (IP3Rs), the main Ca2+ release channels located in endoplasmic reticulum (ER) membranes, are known to direct various cellular events such as autophagy and apoptosis. Here we investigated the intracellular Ca2+-mediated regulation of survival and death of adult hippocampal neural stem (HCN) cells utilizing an insulin withdrawal model of autophagic cell death (ACD). Despite comparable expression levels of RyR and IP3R transcripts in HCN cells at normal state, the expression levels of RyRs—especially RyR3—were markedly upregulated upon insulin withdrawal. While treatment with the RyR agonist caffeine significantly promoted the autophagic death of insulin-deficient HCN cells, treatment with its inhibitor dantrolene prevented the induction of autophagy following insulin withdrawal. Furthermore, CRISPR/Cas9-mediated knockout of the RyR3 gene abolished ACD of HCN cells. This study delineates a distinct, RyR3-mediated ER Ca2+regulation of autophagy and programmed cell death in neural stem cells. Our findings provide novel insights into the critical, yet understudied mechanisms underlying the regulatory function of ER Ca2+ in neural stem cell biology. © 2016 Chung, Jeong, Park, An and Yu.
URI
http://hdl.handle.net/20.500.11750/2687
DOI
10.3389/fncel.2016.00116
Publisher
Frontiers Research Foundation
Related Researcher
Files:
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Collection:
Brain and Cognitive SciencesLaboratory of Neuronal Cell Death1. Journal Articles
Brain and Cognitive SciencesETC1. Journal Articles
Brain and Cognitive SciencesETC1. Journal Articles


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