Abstract
β-N-Oxalylamino-L-alanine (L-BOAA), a nonprotein 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.
Original language | English (US) |
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Pages (from-to) | 1842-1848 |
Number of pages | 7 |
Journal | Journal of neurochemistry |
Volume | 65 |
Issue number | 4 |
State | Published - Oct 1995 |
Keywords
- AMPA
- NADH-dehydrogenase
- β-N-Oxalylamino-L-alanine
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience
- Biochemistry