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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
|
pubmed:dateCreated |
1995-10-25
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pubmed:abstractText |
beta-N-Oxalylamino-L-alanine (L-BOAA), a non-protein neuroexcitatory amino acid present in the seeds of Lathyrus sativus (chickling or grass pea), is known to produce its neurotoxic effects by overstimulation of non-N-methyl-D-aspartate receptors, especially alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors, at micromolar concentrations. It has recently been reported that L-BOAA selectively inhibits mitochondrial enzyme NADH-dehydrogenase (NADH-DH) in brain slices at subpicomolar concentrations. The present study finds that up to 4 mM concentrations of pure L-BOAA fail to inhibit NADH-DH activity in mouse brain homogenate and isolated brain mitochondria. Two known inhibitors (rotenone and 1-methyl-4-phenylpyridinium ion, MPP+) of this mitochondrial enzyme produced significant inhibition under identical conditions. NADH-DH inhibition was also not observed in the homogenate or mitochondria from the brains of animals systemically treated with convulsive doses of L-BOAA. Some inhibition (20-37%) of NADH-DH activity was observed in mouse brain slices incubated with 100-1,000 microM concentrations of L-BOAA for 1 h at 37 degrees C in an atmosphere of 95% O2 and 5% CO2, but the inhibition was nonselective, because the activity of another mitchondrial enzyme, succinic dehydrogenase, was similarly inhibited by L-BOAA. These results are in contrast with the report that L-BOAA inhibits mitochondrial NADH-DH selectively at subpicomolar concentrations. We suggest the observed nonselective NADH-DH inhibition in mouse brain slices treated with L-BOAA is caused by neuronal damage through an excitotoxic mechanism.
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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/Amino Acids, Diamino,
http://linkedlifedata.com/resource/pubmed/chemical/L-Lactate Dehydrogenase,
http://linkedlifedata.com/resource/pubmed/chemical/NADH Dehydrogenase,
http://linkedlifedata.com/resource/pubmed/chemical/beta-Alanine,
http://linkedlifedata.com/resource/pubmed/chemical/oxalyldiaminopropionic acid
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0022-3042
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pubmed:author | |
pubmed:issnType |
Print
|
pubmed:volume |
65
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pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
1842-8
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:7561883-Aging,
pubmed-meshheading:7561883-Amino Acids, Diamino,
pubmed-meshheading:7561883-Animals,
pubmed-meshheading:7561883-Brain,
pubmed-meshheading:7561883-L-Lactate Dehydrogenase,
pubmed-meshheading:7561883-Male,
pubmed-meshheading:7561883-Mice,
pubmed-meshheading:7561883-Mice, Inbred Strains,
pubmed-meshheading:7561883-NADH Dehydrogenase,
pubmed-meshheading:7561883-beta-Alanine
|
pubmed:year |
1995
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pubmed:articleTitle |
Action of beta-N-oxalylamino-L-alanine on mouse brain NADH-dehydrogenase activity.
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pubmed:affiliation |
Center for Research on Occupational and Environmental Toxicology, Oregon Health Sciences University, Portland 97201, USA.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|