Document Detail

The toxic responses induced by okadaic acid involve processing of multiple caspase isoforms.
MedLine Citation:
PMID:  11137534     Owner:  NLM     Status:  MEDLINE    
The recognized role of caspases as executioners of apoptosis, led us to investigate their involvement in death responses induced by okadaic acid (OA) in HeLa S(3) and MCF-7 cells. A one-day treatment with OA induced accumulation of the 85kDa poly(ADP-ribose) polymerase (PARP) fragment in cell lysates but the response was prevented if cells were treated with OA in the presence of the caspase inhibitors Z-VAD-FMK and Z-DEVD-FMK. The HeLa S(3) and MCF-7 cells were found to contain measurable levels of the intact caspase-2, -7, -8 and -9 zymogens, whereas caspase-3 was found only in HeLa cells. After one day of OA treatment, pro-caspase-2, -3, -7 and -9 isoforms were found processed in HeLa cells, whereas only pro-caspase-2 was processed in MCF-7 cells. Pro-caspase-8, in turn, was mostly unprocessed in both cell lines. The possible interference of caspase inhibitors on cell death was also evaluated, and we found that both Z-VAD-FMK and Z-DEVD-FMK could contribute different extents of protection of MCF-7 and HeLa cells from toxic effects caused by OA. We concluded that OA triggers multiple pathways of caspase processing, contributing to death responses triggered by OA in HeLa S(3) and MCF-7 cells.
G P Rossini; N Sgarbi; C Malaguti
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Toxicon : official journal of the International Society on Toxinology     Volume:  39     ISSN:  0041-0101     ISO Abbreviation:  Toxicon     Publication Date:  2001 Jun 
Date Detail:
Created Date:  2001-01-26     Completed Date:  2001-03-08     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  1307333     Medline TA:  Toxicon     Country:  England    
Other Details:
Languages:  eng     Pagination:  763-70     Citation Subset:  IM    
Dipartimento di Scienze Biomediche, Sezione di Chimica Biologica, Università di Modena e Reggio Emilia, Via Campi 287, 41100 Modena, Italy.
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MeSH Terms
Blotting, Western
Caspases / metabolism*
Electrophoresis, Polyacrylamide Gel
Isoenzymes / metabolism*
Okadaic Acid / toxicity*
Protein Processing, Post-Translational*
Tumor Cells, Cultured
Reg. No./Substance:
0/Isoenzymes; 78111-17-8/Okadaic Acid; EC 3.4.22.-/Caspases

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