Document Detail


Role of endonuclease G in senescence-associated cell death of human endothelial cells.
MedLine Citation:
PMID:  20211237     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Mitotic cells in culture show a limited replicative potential and after extended subculturing undergo a terminal growth arrest termed cellular senescence. When cells reach the senescent phenotype, this is accompanied by a significant change in the cellular phenotype and massive changes in gene expression, including the upregulation of secreted factors. In human fibroblasts, senescent cells also acquire resistance to apoptosis. In contrary, in human endothelial cells, both replicative and stress-induced premature senescence is accompanied by increased cell death; however mechanisms of cell death are poorly explored. In this communication, we addressed the role of endonuclease G (EndoG), a mitochondrial mediator of caspase-independent cell death, in senescence-associated cell death of human endothelial cells. Using immunofluorescence microscopy, we found, that EndoG is localized in the mitochondria in young cells, but relocalizes to the nucleus upon senescence. When EndoG gene expression was downregulated by lentiviral shRNA vectors, we found a significant reduction in the replicative life span and a corresponding increase in cell death. We also observed a slight shift in the cell death phenotype from necrosis to apoptosis. Together these observations suggest an important role of EndoG in the senescence program of human endothelial cells.
Authors:
Thomas Diener; Michael Neuhaus; Rafal Koziel; Lucia Micutkova; Pidder Jansen-Dürr
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-03-06
Journal Detail:
Title:  Experimental gerontology     Volume:  45     ISSN:  1873-6815     ISO Abbreviation:  Exp. Gerontol.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-06-01     Completed Date:  2010-09-14     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0047061     Medline TA:  Exp Gerontol     Country:  England    
Other Details:
Languages:  eng     Pagination:  638-44     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2010 Elsevier Inc. All rights reserved.
Affiliation:
Institute for Biomedical Aging Research, Austrian Academy of Sciences, Rennweg 10, Innsbruck, Austria.
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MeSH Terms
Descriptor/Qualifier:
Active Transport, Cell Nucleus
Aging / genetics,  metabolism
Apoptosis / genetics*,  physiology*
Cell Aging / genetics*,  physiology*
Cells, Cultured
Endodeoxyribonucleases / antagonists & inhibitors,  genetics*,  metabolism*
Endothelial Cells / cytology*,  enzymology*
Gene Expression
Gene Knockdown Techniques
Humans
Lentivirus / genetics
Membrane Potential, Mitochondrial
Necrosis / enzymology,  genetics,  pathology
RNA, Small Interfering / genetics
Chemical
Reg. No./Substance:
0/RNA, Small Interfering; EC 3.1.-/Endodeoxyribonucleases; EC 3.1.21.-/endonuclease G

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