Document Detail


Poly(adenosine diphosphate ribose) polymerase inhibition prevents necrosis induced by H2O2 but not apoptosis.
MedLine Citation:
PMID:  7615196     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
A J Watson; J N Askew; R S Benson
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Gastroenterology     Volume:  109     ISSN:  0016-5085     ISO Abbreviation:  Gastroenterology     Publication Date:  1995 Aug 
Date Detail:
Created Date:  1995-08-22     Completed Date:  1995-08-22     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0374630     Medline TA:  Gastroenterology     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  472-82     Citation Subset:  AIM; IM    
Affiliation:
Department of Medicine, Hope Hospital, University of Manchester, Salford, England.
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MeSH Terms
Descriptor/Qualifier:
Aminobenzoic Acids / 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:
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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