| Selective disruption of lysosomes in HeLa cells triggers apoptosis mediated by cleavage of Bid by multiple papain-like lysosomal cathepsins. | |
| | |
MedLine Citation:
|
PMID: 14581476 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Increasing evidence suggests that lysosomal proteases are actively involved in apoptosis. Using HeLa cells as the model system, we show that selective lysosome disruption with L-leucyl-L-leucine methyl ester results in apoptosis, characterized by translocation of lysosomal proteases into the cytosol and by the cleavage of a proapoptotic Bcl-2-family member Bid. Apoptosis and Bid cleavage, but not translocation of lysosomal proteases to the cytosol, could be prevented by 15 microM L-trans-epoxysuccinyl(OEt)-Leu-3-methylbutylamide, an inhibitor of papain-like cysteine proteases. Incubation of cells with 15 microM N-benzoyloxycarbonyl-VAD-fluoromethyl ketone prevented apoptosis but not Bid cleavage, suggesting that cathepsin-mediated apoptosis in this system is caspase-dependent. In vitro experiments performed at neutral pH showed that papain-like cathepsins B, H, L, S, and K cleave Bid predominantly at Arg(65) or Arg(71). No Bid cleavage was observed with cathepsins C and X or the aspartic protease cathepsin D. Incubation of full-length Bid treated with cathepsins B, H, L, and S resulted in rapid cytochrome c release from isolated mitochondria. Thus, Bid may be an important mediator of apoptosis induced by lysosomal disruption. |
| | |
Authors:
|
Tina Cirman; Kristina Oresić; Gabriela Droga Mazovec; Vito Turk; John C Reed; Richard M Myers; Guy S Salvesen; Boris Turk |
Related Documents
:
|
9264376 - Camptothecin-induced apoptosis in p53-null human leukemia hl60 cells and their isolated... 19191576 - Proteolytic cleavage of p70 ribosomal s6 kinase by caspase-3 during dna damage-induced ... 15613236 - Hypoxia-mediated apoptosis in oral carcinoma cells occurs via two independent pathways. 22410266 - Immunology of bovine respiratory syncytial virus infection of cattle. 7538996 - Sp-induced contraction of airway smooth muscle in normal and allergen-sensitized rabbit... 16045726 - Immunological profile of peripheral blood lymphocytes and monocytes/macrophages in kawa... |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. Date: 2003-10-27 |
Journal Detail:
|
Title: The Journal of biological chemistry Volume: 279 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 2004 Jan |
Date Detail:
|
Created Date: 2004-01-26 Completed Date: 2004-03-11 Revised Date: 2007-11-14 |
Medline Journal Info:
|
Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
|
Languages: eng Pagination: 3578-87 Citation Subset: IM |
Affiliation:
|
Department of Biochemistry and Molecular Biology, Jozef Stefan Institute, Jamova 39, 1000 Ljubljana, Slovenia. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Apoptosis* BH3 Interacting Domain Death Agonist Protein Carrier Proteins / metabolism, physiology* Caspase 8 Caspases / metabolism Cathepsins / metabolism* Cell Line Cell Line, Tumor Cytochromes c / metabolism Cytosol / metabolism Flow Cytometry Hela Cells Humans Hydrogen-Ion Concentration Liver / metabolism Lysosomes / metabolism* Mice Mitochondria / metabolism Models, Biological Models, Molecular Myocardium / metabolism Papain / chemistry* Protein Structure, Secondary Protein Transport Recombinant Proteins / metabolism Temperature Transfection |
| Grant Support | |
ID/Acronym/Agency:
|
GM60554/GM/NIGMS NIH HHS; NS37878/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/BH3 Interacting Domain Death Agonist Protein; 0/BID protein, human; 0/Bid protein, mouse; 0/Carrier Proteins; 0/Recombinant Proteins; 9007-43-6/Cytochromes c; EC 3.4.-/Cathepsins; EC 3.4.22.-/CASP8 protein, human; EC 3.4.22.-/Casp8 protein, mouse; EC 3.4.22.-/Caspase 8; EC 3.4.22.-/Caspases; EC 3.4.22.2/Papain |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: A sodium zinc exchange mechanism is mediating extrusion of zinc in mammalian cells.
Next Document: Secreted frizzled-related protein 1 (SFRP1) protects fibroblasts from ceramide-induced apoptosis.