Action of β‐N‐Oxalylamino‐l‐Alanine on Mouse Brain NADH‐Dehydrogenase Activity

Mohammad I. Sabri, Barbara Lystrup, Dwijendra N. Roy, Peter S. Spencer

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1842-1848
Number of pages7
JournalJournal of neurochemistry
Volume65
Issue number4
DOIs
StatePublished - Oct 1995

Keywords

  • AMPA
  • NADH‐dehydrogenase
  • β‐N‐Oxalylamino‐l‐alanine

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Action of β‐N‐Oxalylamino‐l‐Alanine on Mouse Brain NADH‐Dehydrogenase Activity'. Together they form a unique fingerprint.

  • Cite this