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It has been suggested that beta-N-oxalylamino-L-alanine, a non-protein amino acid present in the Lathyrus Sativus seeds, may play a role in the etiopathogenesis of neurolathyrism, a toxic form of motor neuron disease clinically characterized by a severe spastic paraparesis. In order to investigate the mechanisms of beta-N-oxalylamino-L-alanine-mediated cell death, we studied the effect of this neurotoxin as well as other excitatory amino acids agonists on the growth and survival of motoneuron hybrid ventral spinal cord 4.1 cells. beta-N-oxalylamino-L-alanine was toxic to ventral spinal cord 4.1 cells in a concentration-dependent fashion (0.5-10 mM). Among the excitatory amino acids tested, only glutamate (1-10 mM), quisqualate (1 mM) and, with less extent, beta-N-methylamino-L-alanine (10 mM) induced a significant reduction of cell survival. The effect of Lathyrus Sativus neurotoxin was a slow process, becoming apparent only after 24-48 h of incubation. Interestingly, a mathematical analysis applied to the time course and dose curve of beta-N-oxalylamino-L-alanine toxicity suggested that even for very low concentrations of the amino acid it is theoretically possible to predict a time-dependent effect. The cell death was not blocked by antagonists of N-methyl-D-aspartate or non-N-methyl-D-aspartate receptors; aurintricarboxylic acid and alpha-tocopherol gave a partial protection; cysteine (1 mM) prevented the toxic effect of both Lathyrus Sativus neurotoxin and glutamate as well as quisqualate. Morphologically, in the presence of either beta-N-oxalylamino-L-alanine, glutamate or quisqualate, ventral spinal cord 4.1 cells showed apoptotic features also confirmed by ISEL technique and agarose gel electrophoresis of genomic DNA. Thus, our results suggest that in ventral spinal cord 4.1 motoneuron hybrid cells, in the absence of functional synaptic excitatory amino acid receptors, beta-N-oxalylamino-L-alanine induces cell degeneration through an apoptotic mechanism, possibly mediated by a block of cystine/glutamate Xc antiporter.
V La Bella, and
M E Alexianu, and
L V Colom, and
A Ionescu, and
A H Mohamed, and
S H Appel
September 1989,
Journal of neurochemistry,
V La Bella, and
M E Alexianu, and
L V Colom, and
A Ionescu, and
A H Mohamed, and
S H Appel
September 1989,
Brain research,
V La Bella, and
M E Alexianu, and
L V Colom, and
A Ionescu, and
A H Mohamed, and
S H Appel
September 1990,
Journal of neurochemistry,
V La Bella, and
M E Alexianu, and
L V Colom, and
A Ionescu, and
A H Mohamed, and
S H Appel
October 1995,
Journal of neurochemistry,
V La Bella, and
M E Alexianu, and
L V Colom, and
A Ionescu, and
A H Mohamed, and
S H Appel
February 1993,
Neurochemical research,
V La Bella, and
M E Alexianu, and
L V Colom, and
A Ionescu, and
A H Mohamed, and
S H Appel
December 1994,
Neuroscience letters,
V La Bella, and
M E Alexianu, and
L V Colom, and
A Ionescu, and
A H Mohamed, and
S H Appel
October 1997,
Journal of neurochemistry,
V La Bella, and
M E Alexianu, and
L V Colom, and
A Ionescu, and
A H Mohamed, and
S H Appel
March 1985,
Journal of neurochemistry,
V La Bella, and
M E Alexianu, and
L V Colom, and
A Ionescu, and
A H Mohamed, and
S H Appel
May 2009,
Journal of neurochemistry,
V La Bella, and
M E Alexianu, and
L V Colom, and
A Ionescu, and
A H Mohamed, and
S H Appel
February 1963,
The Journal of biological chemistry,
