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Valosin-Containing Protein (VCP)/p97 is a key mediator between autopahgic cell death and apoptosis in adult hippocampal neural stem cells followin insulin withdrawal

Valosin-Containing Protein (VCP)/p97 is a key mediator between autopahgic cell death and apoptosis in adult hippocampal neural stem cells followin insulin withdrawal
Yeo, Bo Kyoung
DGIST Authors
Yeo, Bo Kyoung; Yu, Seong Woon; Jang, Jae Eun
Yu, Seong Woon
Jang, Jae Eun
Issue Date
Available Date
Degree Date
2015. 8
Autophagic cell deathApoptosisAdult neural stem cellsInsulin withdrawalValosin-Containing Protein/p97
Programmed cell death (PCD) plays essential roles in regulation of survival and function of neural stem cells (NSCs). Abnormal regulation of this process is associated with aging and neurodegenerative diseases. However, the mechanisms underlying the PCD of NSCs remain largely unknown. Therefore, understanding the mechanism of PCD in NSCs is crucial for exploring therapeutic strategy for the treatment of neurodegenerative diseases. We have previously reported that adult rat hippocampal neural stem (HCN) cells undergo autophagic cell death (ACD) following insulin withdrawal without apoptotic signs despite their normal apoptotic capabilities. It is unknown how interconnection between ACD and apoptosis is mediated in insulin-deprived HCN cells. Valosin-containing protein (VCP)/p97 is known to be essential for autophagosome maturation in mammalian cells. In this study, we report that VCP regulates the rate of autophagic flux in HCN cells following insulin withdrawal, suggesting the novel roles of VCP at other steps of autophagy as well as maturation. Particularly, VCP is expressed abundantly in HCN cells compared to hippocampal tissue and neurons. Pharmacological and genetic inhibition of VCP significantly decreased ACD and autophagy markers, while apoptotic cell death was induced in insulin-depleted HCN cells. Taken together, these data demonstrate that VCP may play an essential role in completion of ACD and mediation of crosstalk between ACD and apoptosis in HCN cells following insulin withdrawal. Elucidating the mechanism by which VCP regulates the crosstalk of ACD and apoptosis will contribute to understanding the molecular mechanism of PCD in NSCs. ⓒ 2015 DGIST
Table Of Contents
1. INTRODUCTION 1 -- 2. Material and methods 3-- 2.1 Antibodies and reagents 3 -- 2.2 Cell culture 3 -- 2.3 Plasmids, siRNA and Transfection 3 -- 2.4 Cell death assay 4 -- 2.5 Western blotting 4 -- 2.6 Quantitative reverse transcription polymerase chain reaction (qRT-PCR) 5 -- 2.7 Annexin V staining and flow cytometry analysis 5 -- 2.8 Statistic analysis 5 -- 3. Results 6-- 3.1 VCP is degraded through autophagy in HCN cells following insulin withdrawal 6 -- 3.2 Inhibition of VCP switched autophagic cell death to apoptosis in insulin depleted HCN cells 6 -- 3.3 Inhibition of VCP significantly reduced autophagic flux in HCN cells following insulin withdrawal 7 -- 3.4 VCP regulates autophagy initiation signaling in insulin-deprived HCN cells 8 -- 4. Discussion 9 -- 5. Figure legends 11 -- 6. Figures 13 -- References 22 -- Abstract in Korean 24 -- Acknowledgement 25
Brain and Cognitive Sciences
Brain and Cognitive SciencesThesesMaster

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