ISSN:
1471-4159
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Abstract: β-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 α-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 µM concentrations of l-BOAA for 1 h at 37°C in an atmosphere of 95% O2 and 5% CO2, but the inhibition was nonselective, because the activity of another mitochondrial 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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1046/j.1471-4159.1995.65041842.x
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