| Internucleosomal DNA cleavage in apoptotic WEHI 231 cells is mediated by a chymotrypsin-like protease. | |
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MedLine Citation:
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PMID: 15507121 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Although several lines of evidence support a role for serine proteases in apoptosis, little is known about the mechanisms involved. In the present study, we have examined the apoptosis-inducing potential and dissected the death-signalling pathways of N-tosyl-L-phenylalanine chloromethyl ketone (TPCK) and N-tosyl-L-lysine chloromethyl ketone (TLCK), inhibitors of chymotrypsin- and trypsin-like proteases, respectively. Our results designate two distinct roles for serine proteases. Firstly, we show that both inhibitors induce biochemical and morphological characteristics of apoptosis, including proteolysis of poly(ADP-ribose) polymerase 1 (PARP-1) and inhibitor of caspase-activated DNase (ICAD), as well as mitochondrial dysfunction, and that their action is abrogated by the caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp.fluoromethylketone (z-VAD.fmk). These results suggest that inhibition of anti-apoptotic serine proteases governs the onset of the caspase-dependant apoptotic cascade. Secondly, we also demonstrate the involvement of a serine protease in the terminal stage of apoptosis. We showed that chymotrypsin-like protease activity is required for internucleosomal DNA fragmentation in apoptotic cells. Hence, DNA fragmentation is abrogated in TPCK-pre-treated WEHI 231 cells undergoing apoptosis triggered either by anti-IgM or TLCK. These results indicate that internucleosomal DNA cleavage in apoptotic cells is mediated by a chymotrypsin-like protease. |
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Authors:
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Jernej Murn; Uros Urleb; Irena Mlinaric-Rascan |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Genes to cells : devoted to molecular & cellular mechanisms Volume: 9 ISSN: 1356-9597 ISO Abbreviation: Genes Cells Publication Date: 2004 Nov |
Date Detail:
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Created Date: 2004-10-27 Completed Date: 2005-04-11 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9607379 Medline TA: Genes Cells Country: England |
Other Details:
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Languages: eng Pagination: 1103-11 Citation Subset: IM |
Affiliation:
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Faculty of Pharmacy, University of Ljubljana, Askerceva 7, 1000 Ljubljana, Slovenia. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis* Blotting, Western Caspases / metabolism Cell Line DNA / metabolism* Enzyme Activation Flow Cytometry Hydrolysis Membrane Potentials Permeability Serine Endopeptidases / metabolism* |
| Chemical | |
Reg. No./Substance:
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9007-49-2/DNA; EC 3.4.21.-/Serine Endopeptidases; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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