Sulfur amino acids deficiency caused by grass pea diet plays an important role in the toxicity of L-β-ODAP by increasing the oxidative stress: studies on a motor neuron cell line.
Neurolathyrism is a motor neuron disease caused by the overconsumption of grass pea (Lathyrus sativus L.) containing L-β-ODAP. The precise mechanism to cause motor neuron degeneration has yet to be elucidated, but should agree with the epidemiological backgrounds. Considering the amino acid content of the legume, and the epidemiological link with prolonged unbalanced nutrition, the shortage of sulfur amino acids methionine and cysteine could affect the toxicity of L-β-ODAP. We analyzed the effect of these amino acids in the media on the toxicity using primary motor neuron culture and a motor neuron cell line NSC-34. Deprivation of both methionine and cysteine exacerbated the toxicity of L-β-ODAP by 66% compared to the complete medium. The glutathione content of these cells was greatly decreased in sulfur amino acid-deprived medium. L-β-ODAP further lowered the content in the deprived media to be 32-44% of the controls compared to normal media being 62-74%. The increased motor neuron toxicity in this medium was neutralized by the addition of reduced glutathione ethyl ester or N-acetylcysteine suggesting the importance of the mitochondrial oxidative stress induced by L-β-ODAP under sulfur amino acid-deficient conditions.
Kusama-Eguchi
Kuniko
K
Research Unit of Biochemistry, School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi, Chiba 274-8555, Japan. kusama.kuniko@nihon-u.ac.jp
Yoshino
Naduki
N
Minoura
Ai
A
Watanabe
Kazuko
K
Kusama
Tadashi
T
Lambein
Fernand
F
Ikegami
Fumio
F
D000111:Acetylcysteine / Q000378:metabolism; D000599:Amino Acids, Diamino / Q000633:toxicity*; D000603:Amino Acids, Sulfur / Q000172:deficiency*; D000818:Animals; D002460:Cell Line; D004032:Diet; D005978:Glutathione / Q000378:metabolism; D007842:Lathyrism / Q000139:chemically induced*; D027807:Lathyrus / Q000737:chemistry; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D009046:Motor Neurons / Q000378:metabolism; D009498:Neurotoxins / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar
D000599:Amino Acids, Diamino; D000603:Amino Acids, Sulfur; D009498:Neurotoxins; C100126:oxalyldiaminopropionic acid; D005978:Glutathione; D000111:Acetylcysteine