Source:http://linkedlifedata.com/resource/pubmed/id/16998864
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
8
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| pubmed:dateCreated |
2006-10-3
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| pubmed:abstractText |
Organic hydroperoxides are produced in the eicosanoid metabolism and by lipid peroxidation. To examine the contribution of glutathione peroxidase-1 (GPx1) and glutathione (GSH) in the disposal of organic hydroperoxides in brain astrocytes, primary astrocyte cultures from wild type or GPx1-deficient (GPx1(-/-)) mice were exposed to cumene hydroperoxide (CHP). After application of 100 microM CHP, the peroxide disappeared quickly from the incubation medium of wild type cells with a half-life of 9 min, whereas CHP clearance was strongly retarded in GPx1(-/-) astrocytes. Depletion of GSH by pre-incubation with buthionine sulfoximine (BSO) significantly slowed CHP clearance by wild type astrocytes, while almost completely preventing peroxide disposal by GPx1(-/-) cells. In contrast, the catalase inhibitor 3-aminotriazole (3AT) had no effect on CHP clearance. Application of CHP to wild type astrocytes was followed by a rapid and transient accumulation of GSSG, whereas in GPx1(-/-) cells no increase in the GSSG content was detected. Astrocytes from both mouse lines remained viable for up to 24 h following CHP exposure, however depletion of cellular GSH by pre-treatment with BSO compromised the viability of astrocytes, an effect that was stronger in GPx1(-/-) than in wild type cells. This cell death was almost completely prevented by iron chelators, whereas pre-incubation with iron increased CHP toxicity. These novel data demonstrate that the toxicity of organic hydroperoxides in astrocytes is iron-mediated, and that an intact GSH system is required for the effective removal of organic hydroperoxides and for protection from these peroxides.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Benzene Derivatives,
http://linkedlifedata.com/resource/pubmed/chemical/Buthionine Sulfoximine,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione Peroxidase,
http://linkedlifedata.com/resource/pubmed/chemical/Iron,
http://linkedlifedata.com/resource/pubmed/chemical/Iron Chelating Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Lipid Peroxides,
http://linkedlifedata.com/resource/pubmed/chemical/Oxidants,
http://linkedlifedata.com/resource/pubmed/chemical/Reactive Oxygen Species,
http://linkedlifedata.com/resource/pubmed/chemical/cumene hydroperoxide,
http://linkedlifedata.com/resource/pubmed/chemical/glutathione peroxidase GPX1
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| pubmed:status |
MEDLINE
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| pubmed:month |
Dec
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| pubmed:issn |
0894-1491
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| pubmed:author | |
| pubmed:copyrightInfo |
(c) 2006Wiley-Liss, Inc.
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| pubmed:issnType |
Print
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| pubmed:volume |
54
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
873-9
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| pubmed:meshHeading |
pubmed-meshheading:16998864-Animals,
pubmed-meshheading:16998864-Animals, Newborn,
pubmed-meshheading:16998864-Astrocytes,
pubmed-meshheading:16998864-Benzene Derivatives,
pubmed-meshheading:16998864-Brain,
pubmed-meshheading:16998864-Buthionine Sulfoximine,
pubmed-meshheading:16998864-Cell Survival,
pubmed-meshheading:16998864-Cells, Cultured,
pubmed-meshheading:16998864-Enzyme Inhibitors,
pubmed-meshheading:16998864-Glutathione,
pubmed-meshheading:16998864-Glutathione Peroxidase,
pubmed-meshheading:16998864-Iron,
pubmed-meshheading:16998864-Iron Chelating Agents,
pubmed-meshheading:16998864-Lipid Peroxides,
pubmed-meshheading:16998864-Metabolic Clearance Rate,
pubmed-meshheading:16998864-Mice,
pubmed-meshheading:16998864-Mice, Inbred C57BL,
pubmed-meshheading:16998864-Oxidants,
pubmed-meshheading:16998864-Oxidative Stress,
pubmed-meshheading:16998864-Reactive Oxygen Species
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| pubmed:year |
2006
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| pubmed:articleTitle |
Glutathione peroxidase 1 and a high cellular glutathione concentration are essential for effective organic hydroperoxide detoxification in astrocytes.
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| pubmed:affiliation |
School of Psychology, Psychiatry, and Psychological Medicine, Monash University, Clayton, Victoria, Australia. jeff.liddell@med.monash.edu.au
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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