| Cathepsin B mediates tumor necrosis factor-induced arachidonic acid release in tumor cells. | |
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MedLine Citation:
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PMID: 12185082 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Arachidonic acid (AA) generated by cytosolic phospholipase A2 (cPLA2) has been suggested to function as a second messenger in tumor necrosis factor (TNF)-induced death signaling. Here, we show that cathepsin B-like proteases are required for the TNF-induced AA release in transformed cells. Pharmaceutical inhibitors of cathepsin B blocked TNF-induced AA release in human breast (MCF-7S1) and cervix (ME-180as) carcinoma as well as murine fibrosarcoma (WEHI-S) cells. Furthermore, TNF-induced AA release was significantly reduced in cathepsin B-deficient immortalized murine embryonic fibroblasts. Employing cPLA2-deficient MCF-7S1 cells expressing ectopic cPLA2 or cPLA2-deficient immortalized murine embryonic fibroblasts, we showed that cPLA2 is dispensable for TNF-induced AA release and death in these cells. Furthermore, TNF-induced cathepsin B-dependent AA release could be dissociated from the cathepsin B-independent cell death in MCF-7S1 cells, whereas both events required cathepsin B activity in other cell lines tested. These data suggest that cathepsin B inhibitors may prove useful not only in the direct control of cell death but also in limiting the damage-associated inflammation. |
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Authors:
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Lasse Foghsgaard; Ulrik Lademann; Dorte Wissing; Birgit Poulsen; Marja Jaattela |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2002-08-15 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 277 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 2002 Oct |
Date Detail:
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Created Date: 2002-10-15 Completed Date: 2002-12-19 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 39499-506 Citation Subset: IM |
Affiliation:
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Apoptosis Laboratory, Institute of Cancer Biology, Danish Cancer Society, Strandboulevarden 49, DK-2100 Copenhagen, Denmark. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Arachidonic Acid / metabolism* Breast Neoplasms / metabolism Caspase 3 Caspases / metabolism Cathepsin B / metabolism* Cathepsin L Cathepsins / metabolism Cell Death Cell Survival Cells, Cultured Cysteine Endopeptidases DNA, Complementary / metabolism Dose-Response Relationship, Drug Female Humans Hydrogen-Ion Concentration Immunoblotting Inflammation Mice Phospholipases A / metabolism Phospholipases A2 Plasmids / metabolism Protein Binding Recombinant Proteins / metabolism Time Factors Transfection Tumor Cells, Cultured Tumor Necrosis Factor-alpha / metabolism* Uterine Cervical Neoplasms / metabolism |
| Chemical | |
Reg. No./Substance:
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0/DNA, Complementary; 0/Recombinant Proteins; 0/Tumor Necrosis Factor-alpha; 506-32-1/Arachidonic Acid; EC 3.1.1.-/Phospholipases A; EC 3.1.1.4/Phospholipases A2; EC 3.4.-/Cathepsins; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Casp3 protein, mouse; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases; EC 3.4.22.-/Cysteine Endopeptidases; EC 3.4.22.1/Cathepsin B; EC 3.4.22.15/CTSL1 protein, human; EC 3.4.22.15/Cathepsin L; EC 3.4.22.15/Ctsl protein, mouse |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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