TY - JOUR
T1 - Apoptosis induced by β-N-oxalylamino-L-alanine on a motoneuron hybrid cell line
AU - La Bella, V.
AU - Alexianu, M. E.
AU - Colom, L. V.
AU - Ionescu, A.
AU - Mohamed, A. H.
AU - Appel, Stanley H.
N1 - Funding Information:
Acknowledgements--This research was supported by grants from the Muscular Dystrophy Association, The M. H. "Jack" Wagner Memorial Fund, and Cephalon, Inc. We thank Dr W.-X. Le for her skilled technical support with the tissue culture work.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 1996/2
Y1 - 1996/2
N2 - It has been suggested that β-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 β-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. β-N-oxalylamino-L-alanine was toxic to ventral spinal cord 4.1 cells in a concentration-dependent fashion 5-10 mM). Among the excitatory amino acids tested, only glutamate (1-10 mM), quisqualate (1 mM) and, with less extent, β-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 β-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 α-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 β-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, β-N-oxalylamino-L-alanine induces cell degeneration through an apoptotic mechanism, possibly mediated by a block of cystine/glutamate Xc̄ antiporter.
AB - It has been suggested that β-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 β-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. β-N-oxalylamino-L-alanine was toxic to ventral spinal cord 4.1 cells in a concentration-dependent fashion 5-10 mM). Among the excitatory amino acids tested, only glutamate (1-10 mM), quisqualate (1 mM) and, with less extent, β-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 β-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 α-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 β-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, β-N-oxalylamino-L-alanine induces cell degeneration through an apoptotic mechanism, possibly mediated by a block of cystine/glutamate Xc̄ antiporter.
KW - β-N-oxalylamino-L-alanine
KW - apoptosis
KW - cysteine
KW - motoneuron hybrid cells
KW - Xc̄ cystine/glutamate antiporter
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U2 - 10.1016/0306-4522(95)00401-7
DO - 10.1016/0306-4522(95)00401-7
M3 - Article
C2 - 8848166
AN - SCOPUS:0029670989
VL - 70
SP - 1039
EP - 1052
JO - Neuroscience
JF - Neuroscience
SN - 0306-4522
IS - 4
ER -