| Generation of an oxidative stress precedes caspase activation during 7beta-hydroxycholesterol-induced apoptosis in U937 cells. | |
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MedLine Citation:
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PMID: 14994280 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The oxysterol 7beta-hydroxycholesterol (7beta-OH) has been shown to induce apoptosis in a number of cell lines. Though not fully elucidated, the mechanism through which this oxysterol induces cell death is thought to involve the generation of an oxidative stress leading to perturbation of the mitochondrion and release of cytochrome c into the cytosol. Cytochrome c together with Apaf-1 causes activation of the initiator caspase, caspase-9, which in turn activates caspase-3 ultimately leading to the degradation of poly(ADP-ribose) polymerase (PARP). The objective of the present study was to investigate the signalling pathway in 7beta-OH-induced apoptosis in U937 cells, a human monocytic blood cell line known to undergo apoptosis upon treatment with 7beta-OH, over a time course of 48 h. Apoptosis was evident after 24 h incubation. Glutathione levels were decreased after 6 h and this was coupled with an increase in SOD activity. Through western blot analysis we examined expression of caspase-3, -8, and -9 and cleavage of the caspase-3 substrate PARP. The sequence proceeded with activation of caspase-9 after 9 h, caspase-3 at the 12 h timepoint, and cleavage of PARP after 24 h treatment with 7beta-OH. Caspase-8 did not appear to play a major role in this particular apoptotic pathway. |
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Authors:
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Lisa Ryan; Yvonne C O'Callaghan; Nora M O'Brien |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of biochemical and molecular toxicology Volume: 18 ISSN: 1095-6670 ISO Abbreviation: J. Biochem. Mol. Toxicol. Publication Date: 2004 |
Date Detail:
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Created Date: 2004-03-02 Completed Date: 2004-10-21 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9717231 Medline TA: J Biochem Mol Toxicol Country: United States |
Other Details:
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Languages: eng Pagination: 50-9 Citation Subset: IM |
Copyright Information:
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Copyright 2004 Wiley Periodicals, Inc. |
Affiliation:
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Department of Food and Nutritional Sciences, University College Cork, Cork, Ireland. |
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* Apoptotic Protease-Activating Factor 1 Caspases / metabolism* Enzyme Activation / drug effects Humans Hydroxycholesterols / toxicity* Oxidative Stress / drug effects* Poly(ADP-ribose) Polymerases / metabolism Proteins / metabolism* Superoxide Dismutase / metabolism U937 Cells |
| Chemical | |
Reg. No./Substance:
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0/APAF1 protein, human; 0/Apoptotic Protease-Activating Factor 1; 0/Hydroxycholesterols; 0/Proteins; 566-26-7/cholest-5-en-3 beta,7 alpha-diol; EC 1.15.1.1/Superoxide Dismutase; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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