| Leukocyte Elastase Inhibitor, the precursor of L-DNase II, inhibits apoptosis by interfering with caspase-8 activation. | |
| | |
MedLine Citation:
|
PMID: 18674571 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
LEI (Leukocyte Elastase Inhibitor), the precursor of the pro-apoptotic molecule L-DNase II, belongs to the ovalbumin subgroup of serpins. Several serpins can inhibit apoptosis: the viral serpin Crm A inhibits Fas or TNFalpha-induced apoptosis, and overexpression of PAI-2 or PI-9 protects cells from TNFalpha or granzyme B induced apoptosis. We have previously shown that LEI overexpression protects cells from etoposide-induced apoptosis. The molecular reason of this anti-apoptotic activity is now investigated. We show that, in BHK-21 and HeLa cells, LEI anti-protease activity is essential for its anti-apoptotic effect. The protease inhibited is cathepsin D, released from the lysosome during etoposide treatment. Cathepsin D enhances caspase activity in the cell by cleaving procaspase-8 and LEI overexpression slows down this cleavage, protecting cells from apoptosis. This let us presume that high expression of LEI in tumor cells may reduce the efficiency of etoposide as a chemotherapeutic agent. |
| | |
Authors:
|
Laura Padrón-Barthe; Jacqueline Courta; Chloé Leprêtre; Atf Nagbou; Alicia Torriglia |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-07-08 |
Journal Detail:
|
Title: Biochimica et biophysica acta Volume: 1783 ISSN: 0006-3002 ISO Abbreviation: Biochim. Biophys. Acta Publication Date: 2008 Oct |
Date Detail:
|
Created Date: 2008-09-09 Completed Date: 2008-11-13 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 0217513 Medline TA: Biochim Biophys Acta Country: Netherlands |
Other Details:
|
Languages: eng Pagination: 1755-66 Citation Subset: IM |
Affiliation:
|
Centre de Recherches des Cordeliers, INSERM, U872, Paris, F-75006, France. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Apoptosis / drug effects* Caspase 6 / metabolism Caspase 8 / antagonists & inhibitors*, metabolism Cathepsin D / metabolism Cell Line Cricetinae Endodeoxyribonucleases / metabolism* Enzyme Activation / drug effects Humans Leukocyte Elastase / antagonists & inhibitors*, chemistry, metabolism Models, Molecular Protein Binding Protein Structure, Tertiary |
| Chemical | |
Reg. No./Substance:
|
EC 3.1.-/Endodeoxyribonucleases; EC 3.1.22.1/deoxyribonuclease II; EC 3.4.21.37/Leukocyte Elastase; EC 3.4.22.-/Caspase 6; EC 3.4.22.-/Caspase 8; EC 3.4.23.5/Cathepsin D |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Flow cytometric detection of progastrin interaction with gastrointestinal cells.
Next Document: Evaluation of isolation methods and RNA integrity for bacterial RNA quantitation.