Regulation of cell death in mitotic neural progenitor cells by asymmetric distribution of prostate apoptosis response 4 (PAR-4) and simultaneous elevation of endogenous ceramide

Hdl Handle:
http://hdl.handle.net/10675.2/550
Title:
Regulation of cell death in mitotic neural progenitor cells by asymmetric distribution of prostate apoptosis response 4 (PAR-4) and simultaneous elevation of endogenous ceramide
Authors:
Bieberich, Erhard; MacKinnon, Sarah; Silva, Jeane; Noggle, Scott A; Condie, Brian G.
Abstract:
Cell death and survival of neural progenitor (NP) cells are determined by signals that are largely unknown. We have analyzed pro-apoptotic signaling in individual NP cells that have been derived from mouse embryonic stem cells. NP formation was concomitant with elevated apoptosis and increased expression of ceramide and prostate apoptosis response 4 (PAR-4). Morpholino oligonucleotide-mediated antisense knockdown of PAR-4 or inhibition of ceramide biosynthesis reduced stem cell apoptosis, whereas PAR-4 overexpression and treatment with ceramide analogs elevated apoptosis. Apoptotic cells also stained for proliferating cell nuclear antigen (a nuclear mitosis marker protein), but not for nestin (a marker for NP cells). In mitotic cells, asymmetric distribution of PAR-4 and nestin resulted in one nestin(â )/PAR-4(+) daughter cell, in which ceramide elevation induced apoptosis. The other cell was nestin(+), but PAR-4(â ), and was not apoptotic. Asymmetric distribution of PAR-4 and simultaneous elevation of endogenous ceramide provides a possible mechanism underlying asymmetric differentiation and apoptosis of neuronal stem cells in the developing brain.
Citation:
J Cell Biol. 2003 Aug 4; 162(3):469-479
Issue Date:
4-Aug-2003
URI:
http://hdl.handle.net/10675.2/550
DOI:
10.1083/jcb.200212067
PubMed ID:
12885759
PubMed Central ID:
PMC2172704
Type:
Article
ISSN:
1540-8140
Appears in Collections:
Institute of Molecular Medicine and Genetics: Faculty Research and Presentations

Full metadata record

DC FieldValue Language
dc.contributor.authorBieberich, Erharden_US
dc.contributor.authorMacKinnon, Sarahen_US
dc.contributor.authorSilva, Jeaneen_US
dc.contributor.authorNoggle, Scott Aen_US
dc.contributor.authorCondie, Brian G.en_US
dc.date.accessioned2012-10-26T16:26:37Z-
dc.date.available2012-10-26T16:26:37Z-
dc.date.issued2003-08-4en_US
dc.identifier.citationJ Cell Biol. 2003 Aug 4; 162(3):469-479en_US
dc.identifier.issn1540-8140en_US
dc.identifier.pmid12885759en_US
dc.identifier.doi10.1083/jcb.200212067en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/550-
dc.description.abstractCell death and survival of neural progenitor (NP) cells are determined by signals that are largely unknown. We have analyzed pro-apoptotic signaling in individual NP cells that have been derived from mouse embryonic stem cells. NP formation was concomitant with elevated apoptosis and increased expression of ceramide and prostate apoptosis response 4 (PAR-4). Morpholino oligonucleotide-mediated antisense knockdown of PAR-4 or inhibition of ceramide biosynthesis reduced stem cell apoptosis, whereas PAR-4 overexpression and treatment with ceramide analogs elevated apoptosis. Apoptotic cells also stained for proliferating cell nuclear antigen (a nuclear mitosis marker protein), but not for nestin (a marker for NP cells). In mitotic cells, asymmetric distribution of PAR-4 and nestin resulted in one nestin(â )/PAR-4(+) daughter cell, in which ceramide elevation induced apoptosis. The other cell was nestin(+), but PAR-4(â ), and was not apoptotic. Asymmetric distribution of PAR-4 and simultaneous elevation of endogenous ceramide provides a possible mechanism underlying asymmetric differentiation and apoptosis of neuronal stem cells in the developing brain.en_US
dc.rightsCopyright © 2003, The Rockefeller University Pressen_US
dc.titleRegulation of cell death in mitotic neural progenitor cells by asymmetric distribution of prostate apoptosis response 4 (PAR-4) and simultaneous elevation of endogenous ceramideen_US
dc.typeArticleen_US
dc.identifier.pmcidPMC2172704en_US
dc.contributor.corporatenameInstitute of Molecular Medicine and Genetics-
dc.contributor.corporatenameDepartment of Medicine-

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