| Synergism of nitric oxide and iron in killing the transformed murine oligodendrocyte cell line N20.1. | |
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MedLine Citation:
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PMID: 10037476 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Nitric oxide (NO) produced in inflammatory lesions may play a major role in the destruction of oligodendrocytes in multiple sclerosis and experimental allergic encephalomyelitis. The transformed murine oligodendroglial line N20.1 is much more resistant than primary oligodendrocytes to killing by the NO generator S-nitroso-N-acetyl-DL-penicillamine (SNAP). This observation prompted investigation of the mechanisms leading to cell death in the N20.1 cells and comparison of SNAP with another NO donor, sodium nitroprusside (SNP). We observed that N20.1 cells were 30 times more sensitive to SNP than to SNAP. The specific NO scavenger 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (PTIO) protected against SNP only, not against SNAP. However, dithiothreitol protected against both SNAP and SNP, indicating that S-nitrosylation of cysteines plays a major role in the cytotoxicity of both NO donors. We did not observe any formation of peroxynitrite or increase of Ca2+ concentration with either SNAP or SNP, thus excluding their involvement in the mechanisms leading to N20.1 cell death. Based on two observations, (a) potentiation of the cytotoxic effect of SNP when coincubated with ferricyanide or ferrocyanide, but not sodium cyanide, and (b) protection by deferoxamine, an iron cyanide chelator, we conclude that the greater sensitivity of N20.1 cells to SNP compared with SNAP is due to synergism between NO released and the iron cyanide portion of SNP, with the cyanide accounting for very little of the cytotoxicity. Finally, SNP but not SNAP induces some apoptosis, as shown by DNA laddering and protection by a caspase-3 inhibitor. These results suggest that low levels of NO in combination with increased iron content lead to apoptotic cell death rather than the necrotic cell death seen with higher levels of NO generated by SNAP. |
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Authors:
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A I Boullerne; L Nedelkoska; J A Benjamins |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Journal of neurochemistry Volume: 72 ISSN: 0022-3042 ISO Abbreviation: J. Neurochem. Publication Date: 1999 Mar |
Date Detail:
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Created Date: 1999-03-18 Completed Date: 1999-03-18 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 2985190R Medline TA: J Neurochem Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 1050-60 Citation Subset: IM |
Affiliation:
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Department of Neurology, Wayne State University, School of Medicine, Detroit, Michigan, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Death / drug effects Cell Line Coloring Agents Culture Media, Serum-Free DNA Fragmentation / drug effects Drug Synergism Immunohistochemistry Iron / antagonists & inhibitors, toxicity* Kinetics Mice Nitrates / metabolism Nitric Oxide / antagonists & inhibitors, physiology*, toxicity Nitric Oxide Donors / antagonists & inhibitors, toxicity Nitroprusside / toxicity Oligodendroglia / drug effects* Oxidants / metabolism Penicillamine / analogs & derivatives, antagonists & inhibitors, toxicity S-Nitroso-N-Acetylpenicillamine Trypan Blue |
| Grant Support | |
ID/Acronym/Agency:
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NS13143/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Coloring Agents; 0/Culture Media, Serum-Free; 0/Nitrates; 0/Nitric Oxide Donors; 0/Oxidants; 10102-43-9/Nitric Oxide; 15078-28-1/Nitroprusside; 26404-66-0/peroxynitric acid; 52-67-5/Penicillamine; 72-57-1/Trypan Blue; 7439-89-6/Iron; 79032-48-7/S-Nitroso-N-Acetylpenicillamine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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