Document Detail


Senescent keratinocytes die by autophagic programmed cell death.
MedLine Citation:
PMID:  19147823     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Normal cells reach senescence after a specific time and number of divisions, leading ultimately to cell death. Although escape from this fate may be a requisite step in neoplastic transformation, the mechanisms governing senescent cell death have not been well investigated. We show here, using normal human epidermal keratinocytes, that no apoptotic markers appear with senescence. In contrast, the expression of several proteins involved in the regulation of macroautophagy, notably Beclin-1 and Bcl-2, was found to change with senescence. The corpses occurring at the senescence growth plateau displayed a large central area delimited by the cytokeratin network that contained a huge quantity of autophagic vacuoles, the damaged nucleus, and most mitochondria. 3-methyladenine, an inhibitor of autophagosome formation, but not the caspase inhibitor zVAD, prevented senescent cell death. We conclude that senescent cells do not die by apoptosis, but as a result of high macroautophagic activity that targets the primary vital cell components.
Authors:
Karo Gosselin; Emeric Deruy; Sébastien Martien; Chantal Vercamer; Fatima Bouali; Thibault Dujardin; Christian Slomianny; Ludivine Houel-Renault; Fazia Chelli; Yvan De Launoit; Corinne Abbadie
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-01-15
Journal Detail:
Title:  The American journal of pathology     Volume:  174     ISSN:  1525-2191     ISO Abbreviation:  Am. J. Pathol.     Publication Date:  2009 Feb 
Date Detail:
Created Date:  2009-01-23     Completed Date:  2009-02-17     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0370502     Medline TA:  Am J Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  423-35     Citation Subset:  AIM; IM    
Affiliation:
UMR8161, Institut de Biologie de Lille, Lille Cedex, France.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis Regulatory Proteins / biosynthesis
Autophagy / physiology*
Blotting, Western
Cell Aging / physiology
Female
Flow Cytometry
Fluorescent Antibody Technique
Gene Expression
Humans
In Situ Nick-End Labeling
Keratinocytes / pathology*,  physiology
Membrane Proteins / biosynthesis
Microscopy, Electron, Transmission
Proto-Oncogene Proteins c-bcl-2 / biosynthesis
Chemical
Reg. No./Substance:
0/Apoptosis Regulatory Proteins; 0/BECN1 protein, human; 0/Membrane Proteins; 0/Proto-Oncogene Proteins c-bcl-2
Comments/Corrections

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