| MnSOD upregulation induces autophagic programmed cell death in senescent keratinocytes. | |
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MedLine Citation:
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PMID: 20856861 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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Senescence is a state of growth arrest resulting mainly from telomere attrition and oxidative stress. It ultimately leads to cell death. We have previously shown that, in keratinocytes, senescence is induced by NF-kappaB activation, MnSOD upregulation and H(2)O(2) overproduction. We have also shown that senescent keratinocytes do not die by apoptosis but as a result of high macroautophagic activity that targets the primary vital cell components. Here, we investigated the mechanisms that activate this autophagic cell death program. We show that corpses occurring at the senescence plateau display oxidatively-damaged mitochondria and nucleus that colocalize with autophagic vacuoles. The occurrence of such corpses was decreased by specifically reducing the H(2)O(2) level with catalase, and, conversely, reproduced by overexpressing MnSOD or applying subtoxic doses of H(2)O(2). This H(2)O(2)-induced cell death did occur through autophagy since it was accompanied by an accumulation of autophagic vesicles as evidenced by Lysotracker staining, LC3 vesiculation and transmission electron microscopy. Most importantly, it was partly abolished by 3-methyladenine, the specific inhibitor of autophagosome formation, and by anti-Atg5 siRNAs. Taken together these results suggest that autophagic cell death is activated in senescent keratinocytes because of the upregulation of MnSOD and the resulting accumulation of oxidative damages to nucleus and mitochondria. |
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Authors:
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Emeric Deruy; Karo Gosselin; Chantal Vercamer; Sébastien Martien; Fatima Bouali; Christian Slomianny; Julie Bertout; David Bernard; Albin Pourtier; Corinne Abbadie |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-09-14 |
Journal Detail:
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Title: PloS one Volume: 5 ISSN: 1932-6203 ISO Abbreviation: PLoS ONE Publication Date: 2010 |
Date Detail:
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Created Date: 2010-09-21 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101285081 Medline TA: PLoS One Country: United States |
Other Details:
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Languages: eng Pagination: e12712 Citation Subset: IM |
Affiliation:
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Université Lille Nord de France, Lille, France. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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