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Autophagic death of adult hippocampal neural stem cells following insulin withdrawal.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Yu, Seong-Woon Baek, Seung-Hoon Brennan, Ryan T. Bradley, Christopher J. Park, Se Kyong Lee, Yoon Sun Jun, Eun Jung Lookingland, Keith J. Kim, Eun-Kyoung Lee, Heuiran Goudreau, John L. Kim, Seong Who
Description	Country affiliation: United States Author Affiliation: Yu SW ( Departments of Neurology and Ophthalmology, Michigan State University, East Lansing, Michigan 48824, USA. Seong-Woon.Yu@ht.msu.edu)
Abstract	Novel therapeutic approaches using stem cell transplantation to treat neurodegenerative diseases have yielded promising results. However, survival of stem cells after transplantation has been very poor in animal models, and considerable efforts have been directed at increasing the viability of engrafted stem cells. Therefore, understanding the mechanisms that regulate survival and death of neural stem cells is critical to the development of stem cell-based therapies. Hippocampal neural (HCN) stem cells derived from the adult rat brain undergo cell death following insulin withdrawal, which is associated with downregulation of antiapoptotic Bcl-2 family members. To understand the type of cell death in HCN cells following insulin withdrawal, apoptosis markers were assessed. Of note, DNA fragmentation or caspase-3 activation was not observed, but rather dying cells displayed features of autophagy, including increased expression of Beclin 1 and the type II form of light chain 3. Electron micrographs showed the dramatically increased formation of autophagic vacuoles with cytoplasmic contents. Staurosporine induced robust activation of caspase-3 and nucleosomal DNA fragmentation, suggesting that the machinery of apoptosis is intact in HCN cells despite the apparent absence of apoptosis following insulin withdrawal. Autophagic cell death was suppressed by knockdown of autophagy-related gene 7, whereas promotion of autophagy by rapamycin increased cell death. Taken together, these data demonstrate that HCN cells undergo a caspase-independent, autophagic cell death following insulin withdrawal. Understanding the mechanisms governing autophagy of adult neural stem cells may provide novel strategies to improve the survival rate of transplanted stem cells for treatment of neurodegenerative diseases. Disclosure of potential conflicts of interest is found at the end of this article.
File Format	HTM / HTML
ISSN	10665099
Issue Number	10
Volume Number	26
e-ISSN	15494918
Journal	STEM CELLS
Language	English
Publisher	Wiley
Publisher Date	2008-10-01
Publisher Place	United States
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Cell Biology Discipline Embryology Adult Stem Cells Cytology Autophagy Hippocampus Insulin Deficiency Neurons Stem Cells Animals Apoptosis Cell Proliferation Cells, Cultured Down-regulation Immunohistochemistry Intermediate Filament Proteins Metabolism Nerve Tissue Proteins Nestin Ultrastructure Rats Vacuoles Bcl-x Protein Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Cell Biology Developmental Biology Medicine Molecular Medicine

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