Document Detail


Generation of free radicals during lipid hydroperoxide-triggered apoptosis in PC12h cells.
MedLine Citation:
PMID:  9084499     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The compound 13-L-hydroperoxylinoleic acid (LOOH) triggered the death of clonal rat pheochromocytoma PC12h cells (LD50 = about 8 microM). LOOH induced nuclear condensation and DNA fragmentation, which was prevented by cycloheximide (a protein synthesis inhibitor) and NGF, indicating that LOOH triggered apoptosis in PC12h cells. LOOH produced reactive oxygen species (ROS) in PC12h cells in a time- and dose-dependent manner, as measured by flow cytometry using the ROS-specific fluorescent indicator, 6-carboxy-2,7-dichorodihydrofluorescein diacetate, di(acetoxymethyl ester) (C-DCDHF-DA). Antioxidants such as N,N'-diphenyl-p-phenylenediamine (DPPD), vitamin E and N-acetylcysteine, and a ferric iron chelator, deferoxamine, inhibited the LOOH-triggered apoptosis and simultaneously decreased the generation of ROS, whereas an inhibitor of glutathione synthesis, buthionine sulfoximine (BSO), enhanced the apoptosis and increased the generation of ROS. These results indicate that LOOH triggers the apoptosis of PC12h cells by increasing the production of ROS. A confocal analysis with the Ca(2+)-specific fluorescent indicator, fluo-3, demonstrated that LOOH at concentrations up to 200 microM, did not increase the intracellular Ca2+ concentration. These data indicate that LOOH induces apoptosis of PC12h cells through the enhanced production of ROS, not through increasing the permeability of Ca2+.
Authors:
H Aoshima; T Satoh; N Sakai; M Yamada; Y Enokido; T Ikeuchi; H Hatanaka
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  1345     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  1997 Mar 
Date Detail:
Created Date:  1997-04-09     Completed Date:  1997-04-09     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  35-42     Citation Subset:  IM    
Affiliation:
Division of Protein Biosynthesis, Osaka University, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis*
Calcium / analysis
Cell Survival
DNA Fragmentation
Flow Cytometry
Free Radicals / chemical synthesis*
Linoleic Acids / pharmacology*
PC12 Cells / drug effects
Rats
Reactive Oxygen Species*
Chemical
Reg. No./Substance:
0/Free Radicals; 0/Linoleic Acids; 0/Reactive Oxygen Species; 34444-18-3/13-hydroperoxylinoleic acid; 7440-70-2/Calcium

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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