| Poly(adenosine diphosphate ribose) polymerase inhibition prevents necrosis induced by H2O2 but not apoptosis. | |
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MedLine Citation:
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PMID: 7615196 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND & AIMS: H2O2 causes DNA damage, which activates poly(adenosine diphosphate ribose) polymerase (PARP), a nuclear enzyme that uses nicotinamide adenine dinucleotide (NAD) as a substrate. When DNA strand breaks are extensive, consumption of NAD by PARP can cause adenosine triphosphate depletion. The aim was to study the effect of PARP inhibition on H2O2-induced cell injury in the intestinal epithelial cell line HT-29-18-C1. METHODS: Cell injury was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide test and flow cytometric analysis. RESULTS: The PARP inhibitors 3-aminobenzamide and nicotinamide both prevented cell death immediately after exposure to 1 mmol/L H2O2 and loss of cellular NAD and adenosine triphosphate. The inactive structural analogues 3-aminobenzoic acid and nicotinic acid had no such protective effect. H2O2 also caused HT-29 cells to detach from the monolayer up to 24 hours after exposure and die by apoptosis in the incubating medium. Flow cytometric analysis showed that 3-aminobenzamide had no effect on this delayed detachment process. CONCLUSIONS: H2O2 induces two distinct death pathways in HT-29 cells: one that is immediate and may represent necrosis and another that is delayed, causing cell detachment leading to apoptosis. PARP inhibition prevents necrosis but has no effect on delayed cell detachment leading to apoptosis. |
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Authors:
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A J Watson; J N Askew; R S Benson |
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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: Gastroenterology Volume: 109 ISSN: 0016-5085 ISO Abbreviation: Gastroenterology Publication Date: 1995 Aug |
Date Detail:
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Created Date: 1995-08-22 Completed Date: 1995-08-22 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0374630 Medline TA: Gastroenterology Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 472-82 Citation Subset: AIM; IM |
Affiliation:
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Department of Medicine, Hope Hospital, University of Manchester, Salford, England. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aminobenzoic Acids
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pharmacology Apoptosis / drug effects* Benzamides / pharmacology* Cell Count / drug effects Cell Line DNA Repair / drug effects Humans Hydrogen Peroxide Intestinal Mucosa / pathology* Necrosis / chemically induced, prevention & control* Niacin / pharmacology Niacinamide / pharmacology* Poly(ADP-ribose) Polymerases / antagonists & inhibitors* Time Factors |
| Chemical | |
Reg. No./Substance:
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0/Aminobenzoic Acids; 0/Benzamides; 3544-24-9/3-aminobenzamide; 59-67-6/Niacin; 7722-84-1/Hydrogen Peroxide; 98-92-0/Niacinamide; 99-05-8/3-aminobenzoic acid; EC 2.4.2.30/Poly(ADP-ribose) Polymerases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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