Source:http://linkedlifedata.com/resource/pubmed/id/11744336
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
12
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| pubmed:dateCreated |
2001-12-17
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| pubmed:abstractText |
Nitroxyl (NO(-)/HNO), has been proposed to be one of the NO(*)-derived cytotoxic species. Although the biological effect of nitroxyl is largely unknown, it has been reported to cause DNA breakage and cytotoxicity. We have therefore investigated whether NO(-)/HNO-induced DNA single-strand breakage activates the nuclear nick sensor enzyme poly(ADP-ribose) polymerase (PARP) and whether PARP activation affects the mode of NO(-)/HNO- induced cell death. NO(-)/HNO generated from Angeli's salt (AS, sodium trioxodinitrate) (0-300 microM) induced DNA single-strand breakage, PARP activation, and a concentration-dependent cytotoxicity in murine thymocytes. AS-induced cell death was also accompanied by decreased mitochondrial membrane potential and increased secondary superoxide production. The cytotoxicity of AS, as measured by propidium iodide uptake, was abolished by electron acceptors potassium ferricyanide, TEMPOL, the intracellular calcium chelator BAPTA-AM, and by PARP inhibitors 3-aminobenzamide (3-AB) and PJ-34. The cytoprotective effect of 3-AB was paralleled by increased output of AS-induced apoptotic parameters such as phosphatidylserine exposure, caspase activation, and DNA fragmentation. No significant increase in tyrosine nitration could be observed in AS-treated thymocytes as opposed to peroxynitrite-treated cells, indicating that tyrosine nitration is not likely to contribute to NO(-)/HNO-induced cytotoxicity. Our results demonstrate that NO(-)/HNO-induced PARP activation shifts the default apoptotic cell death toward necrosis in thymocytes. However, as total PARP inhibition resulted only in 30% cytoprotection, PARP-independent mechanisms dominate NO(-)/HNO-induced cytotoxicity in thymocytes.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/3-aminobenzamide,
http://linkedlifedata.com/resource/pubmed/chemical/Benzamides,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Nitrates,
http://linkedlifedata.com/resource/pubmed/chemical/Nitrites,
http://linkedlifedata.com/resource/pubmed/chemical/Nitrogen Oxides,
http://linkedlifedata.com/resource/pubmed/chemical/Poly(ADP-ribose) Polymerases,
http://linkedlifedata.com/resource/pubmed/chemical/Protective Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine,
http://linkedlifedata.com/resource/pubmed/chemical/nitroxyl,
http://linkedlifedata.com/resource/pubmed/chemical/oxyhyponitrite,
http://linkedlifedata.com/resource/pubmed/chemical/peroxynitric acid
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| pubmed:status |
MEDLINE
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| pubmed:month |
Dec
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| pubmed:issn |
0891-5849
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
15
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| pubmed:volume |
31
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1616-23
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| pubmed:dateRevised |
2007-11-14
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| pubmed:meshHeading |
pubmed-meshheading:11744336-Animals,
pubmed-meshheading:11744336-Apoptosis,
pubmed-meshheading:11744336-Benzamides,
pubmed-meshheading:11744336-Caspases,
pubmed-meshheading:11744336-Cells, Cultured,
pubmed-meshheading:11744336-DNA Damage,
pubmed-meshheading:11744336-DNA Fragmentation,
pubmed-meshheading:11744336-Enzyme Activation,
pubmed-meshheading:11744336-Enzyme Inhibitors,
pubmed-meshheading:11744336-Male,
pubmed-meshheading:11744336-Mice,
pubmed-meshheading:11744336-Mice, Inbred C57BL,
pubmed-meshheading:11744336-Mitochondria,
pubmed-meshheading:11744336-Nitrates,
pubmed-meshheading:11744336-Nitrites,
pubmed-meshheading:11744336-Nitrogen Oxides,
pubmed-meshheading:11744336-Poly(ADP-ribose) Polymerases,
pubmed-meshheading:11744336-Protective Agents,
pubmed-meshheading:11744336-Thymus Gland,
pubmed-meshheading:11744336-Tyrosine
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| pubmed:year |
2001
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| pubmed:articleTitle |
Partial protection by poly(ADP-ribose) polymerase inhibitors from nitroxyl-induced cytotoxity in thymocytes.
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| pubmed:affiliation |
Department of Medical Chemistry, University of Debrecen, Debrecen, Hungary.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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