| Stress-induced apoptosis is impaired in cells with a lysosomal targeting defect but is not affected in cells synthesizing a catalytically inactive cathepsin D. | |
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MedLine Citation:
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PMID: 12934083 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The role of cathepsin D in stress-induced cell death has been investigated by using ovine fibroblasts exhibiting a missense mutation in the active site of cathepsin D. The cathepsin D (lysosomal aspartic protease) deficiency did not protect cells against toxicity induced by doxorubicin and other cytotoxic agents, neither did it protect cells from caspase activation. Moreover, the cathepsin D inhibitor, pepstatin A, did not prevent stress-induced cell death in human fibroblasts or lymphoblasts. The possible role of lysosomal ceramide or sphingosine-mediated activation of cathepsin D in apoptosis was also excluded by using human cells either overexpressing or deficient in acid ceramidase. However, a normal lysosomal function seems to be required for efficient cell death, as indicated by the finding that fibroblasts from patients with mucolipidosis II were partially resistant to staurosporine, sphingosine and TNF-induced apoptosis, suggesting a key role of lysosomes in cell death. |
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Authors:
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C Tardy; J Tyynelä; A Hasilik; T Levade; N Andrieu-Abadie |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Cell death and differentiation Volume: 10 ISSN: 1350-9047 ISO Abbreviation: Cell Death Differ. Publication Date: 2003 Sep |
Date Detail:
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Created Date: 2003-08-22 Completed Date: 2004-04-16 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 9437445 Medline TA: Cell Death Differ Country: England |
Other Details:
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Languages: eng Pagination: 1090-100 Citation Subset: IM |
Affiliation:
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INSERM U466, Institut Louis Bugnard, Centre Hospitalier Universitaire de Rangueil, Toulouse, France. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acid Ceramidase Amidohydrolases / genetics Animals Apoptosis* Caspases / metabolism Catalytic Domain Cathepsin D / biosynthesis, genetics, physiology* Cathepsins / antagonists & inhibitors Cells, Cultured Ceramidases Ceramides / metabolism Doxorubicin / toxicity Fibroblasts / cytology, drug effects, metabolism Humans Lysosomes / enzymology* Mucolipidoses / pathology Mutation, Missense Pepstatins / pharmacology Protease Inhibitors / pharmacology Protein Transport Sheep |
| Chemical | |
Reg. No./Substance:
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0/Ceramides; 0/Pepstatins; 0/Protease Inhibitors; 23214-92-8/Doxorubicin; 39324-30-6/pepstatin; EC 3.4.-/Cathepsins; EC 3.4.22.-/Caspases; EC 3.4.23.5/Cathepsin D; EC 3.5.-/Amidohydrolases; EC 3.5.1.23/ASAH1 protein, human; EC 3.5.1.23/Acid Ceramidase; EC 3.5.1.23/Ceramidases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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