| Role of caspases-3 and -7 in Apaf-1 proteolytic cleavage and degradation events during cisplatin-induced apoptosis in melanoma cells. | |
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MedLine Citation:
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PMID: 14729468 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Apoptosis protease-activating factor-1 (Apaf-1), the central element in the mitochondrial pathway of apoptosis, is frequently absent or poorly expressed in metastatic melanomas, a tumor type showing a low degree of spontaneous apoptosis and a poor response to conventional therapies. In the present study, we used the Apaf-1-positive Me665/2/21 melanoma cell line to investigate the fate of Apaf-1 during cisplatin-induced apoptosis. As novel findings described for the first time in melanoma cells, we observed that Apaf-1 was markedly decreased during apoptosis, already at early stages of cell damage; concurrently, an immunoreactive N-terminal fragment of congruent with 26 kDa was evident. In spite of the remarkable decrease of Apaf-1 in apoptotic cells, caspase-9 was found to be processed and enzymatically active. Both Apaf-1 depletion and its proteolytic cleavage were markedly prevented in presence of the caspase-3/-7 inhibitor ac-DEVD-CHO. In presence of ac-DEVD-CHO, caspase-9 activity was also inhibited, along with a partially different pattern of caspase-9 processing forms. Unexpectedly, the inhibition afforded by ac-DEVD-CHO on several components, that is, caspase-3/-7 and caspase-9 activities, and Apaf-1 proteolytic degradation, did not abrogate the apoptotic morphology and cell detachment, nor the proteolytic degradation of crucial targets, such as poly(ADP-ribose) polymerase (PARP) and lamin B. Together, our results suggest that caspase-3 and -7, proved to be dispensable for the above apoptosis-associated events, play a role on Apaf-1 handling and possibly on apoptosome function. |
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Authors:
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Barbara Del Bello; Marta A Valentini; Paola Mangiavacchi; Mario Comporti; Emilia Maellaro |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Experimental cell research Volume: 293 ISSN: 0014-4827 ISO Abbreviation: Exp. Cell Res. Publication Date: 2004 Feb |
Date Detail:
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Created Date: 2004-01-19 Completed Date: 2004-03-03 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0373226 Medline TA: Exp Cell Res Country: United States |
Other Details:
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Languages: eng Pagination: 302-10 Citation Subset: IM |
Affiliation:
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Department of Pathophysiology, Experimental Medicine and Public Health, University of Siena, via A. Moro, 53100 Siena, Italy. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis
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drug effects*,
physiology Apoptotic Protease-Activating Factor 1 Caspase 3 Caspase 7 Caspases / antagonists & inhibitors, metabolism* Cell Adhesion / drug effects, physiology Cell Line, Tumor Cisplatin / pharmacology* Cytochromes c / metabolism Down-Regulation / drug effects, physiology Drug Resistance, Neoplasm / physiology Enzyme Inhibitors / pharmacology Humans Lamin Type B / metabolism Macromolecular Substances Melanoma / drug therapy, enzymology* Mitochondria / drug effects, enzymology Peptide Fragments / metabolism Peptide Hydrolases / drug effects, metabolism Poly(ADP-ribose) Polymerases Proteins / drug effects, metabolism* Signal Transduction / drug effects, physiology |
| Chemical | |
Reg. No./Substance:
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0/APAF1 protein, human; 0/Apoptotic Protease-Activating Factor 1; 0/Enzyme Inhibitors; 0/Lamin Type B; 0/Macromolecular Substances; 0/Peptide Fragments; 0/Proteins; 15663-27-1/Cisplatin; 9007-43-6/Cytochromes c; EC 2.4.2.30/PARP1 protein, human; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 3.4.-/Peptide Hydrolases; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/CASP7 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspase 7; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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