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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2000-1-27
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pubmed:abstractText |
Glutathione peroxidase (GSHPx) is a critical intracellular enzyme involved in detoxification of hydrogen peroxide (H(2)O(2)) to water. In the present study we examined the susceptibility of mice with a disruption of the glutathione peroxidase gene to the neurotoxic effects of malonate, 3-nitropropionic acid (3-NP), and 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP). Glutathione peroxidase knock-out mice showed no evidence of neuropathological or behavioral abnormalities at 2-3 months of age. Intrastriatal injections of malonate resulted in a significant twofold increase in lesion volume in homozygote GSHPx knock-out mice as compared to both heterozygote GSHPx knock-out and wild-type control mice. Malonate-induced increases in conversion of salicylate to 2,3- and 2, 5-dihydroxybenzoic acid, an index of hydroxyl radical generation, were greater in homozygote GSHPx knock-out mice as compared with both heterozygote GSHPx knock-out and wild-type control mice. Administration of MPTP resulted in significantly greater depletions of dopamine, 3,4-dihydroxybenzoic acid, and homovanillic acid in GSHPx knock-out mice than those seen in wild-type control mice. Striatal 3-nitrotyrosine (3-NT) concentrations after MPTP were significantly increased in GSHPx knock-out mice as compared with wild-type control mice. Systemic 3-NP administration resulted in significantly greater striatal damage and increases in 3-NT in GSHPx knock-out mice as compared to wild-type control mice. The present results indicate that a knock-out of GSHPx may be adequately compensated under nonstressed conditions, but that after administration of mitochondrial toxins GSHPx plays an important role in detoxifying increases in oxygen radicals.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/1-Methyl-4-phenyl-1,2,3,6-tetrahydro...,
http://linkedlifedata.com/resource/pubmed/chemical/2,4-dihydroxybenzylamine,
http://linkedlifedata.com/resource/pubmed/chemical/3,4-Dihydroxyphenylacetic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/3-nitropropionic acid,
http://linkedlifedata.com/resource/pubmed/chemical/3-nitrotyrosine,
http://linkedlifedata.com/resource/pubmed/chemical/Catechols,
http://linkedlifedata.com/resource/pubmed/chemical/Convulsants,
http://linkedlifedata.com/resource/pubmed/chemical/Dopamine Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Free Radicals,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione Peroxidase,
http://linkedlifedata.com/resource/pubmed/chemical/Homovanillic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Malonates,
http://linkedlifedata.com/resource/pubmed/chemical/Nitro Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Propionic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine,
http://linkedlifedata.com/resource/pubmed/chemical/malonic acid
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1529-2401
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
20
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1-7
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:10627575-1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine,
pubmed-meshheading:10627575-3,4-Dihydroxyphenylacetic Acid,
pubmed-meshheading:10627575-Animals,
pubmed-meshheading:10627575-Brain Chemistry,
pubmed-meshheading:10627575-Catechols,
pubmed-meshheading:10627575-Convulsants,
pubmed-meshheading:10627575-Corpus Striatum,
pubmed-meshheading:10627575-Disease Models, Animal,
pubmed-meshheading:10627575-Dopamine Agents,
pubmed-meshheading:10627575-Female,
pubmed-meshheading:10627575-Free Radicals,
pubmed-meshheading:10627575-Glutathione,
pubmed-meshheading:10627575-Glutathione Peroxidase,
pubmed-meshheading:10627575-Heterozygote,
pubmed-meshheading:10627575-Homovanillic Acid,
pubmed-meshheading:10627575-Homozygote,
pubmed-meshheading:10627575-Huntington Disease,
pubmed-meshheading:10627575-MPTP Poisoning,
pubmed-meshheading:10627575-Male,
pubmed-meshheading:10627575-Malonates,
pubmed-meshheading:10627575-Mice,
pubmed-meshheading:10627575-Mice, Inbred Strains,
pubmed-meshheading:10627575-Mice, Knockout,
pubmed-meshheading:10627575-Nitro Compounds,
pubmed-meshheading:10627575-Oxidative Stress,
pubmed-meshheading:10627575-Parkinson Disease, Secondary,
pubmed-meshheading:10627575-Propionic Acids,
pubmed-meshheading:10627575-Tyrosine
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pubmed:year |
2000
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pubmed:articleTitle |
Mice deficient in cellular glutathione peroxidase show increased vulnerability to malonate, 3-nitropropionic acid, and 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine.
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pubmed:affiliation |
Neurology Service, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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