Van Moorhem Marijke, Decrock Elke, De Vuyst Elke, De Bock Marijke, Wang Nan, Lambein Fernand, Van Den Bosch Ludo, Leybaert Luc
Department of Basic Medical Sciences, Physiology Group, Faculty of Medicine and Health Sciences, Ghent University, Gent, Belgium.
Neuroreport. 2011 Feb 16;22(3):131-5. doi: 10.1097/wnr.0b013e3283433027.
The excitatory amino acid L-β-N-oxalyl-α,β-diaminopropionic acid (L-β-ODAP) in Lathyrus sativus L. is proposed as the causative agent of the neurodegenerative disease neurolathyrism. We investigated the effect of L-β-ODAP on [Ca2+]i handling, redox homeostasis, and cell death in rat spinal motor neurons. L-β-ODAP and L-glutamate triggered [Ca2+]i transients, which were inhibited by the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor blockers; 2,3-dioxo-6-nitro-1,2,3, 4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide and 1-naphthyl acetylspermine, the latter specifically blocking Ca2+-permeable α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors. In addition, 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide, and to a lesser extent 1-naphthyl acetylspermine, protected the neurons against cell death induced by L-β-ODAP or L-glutamate. Methionine and cysteine were also protective against neuronal cell death. We conclude that deregulation of [Ca2+]i homeostasis and oxidative stress contribute to motor neuron cell death in neurolathyrism.
香豌豆中的兴奋性氨基酸L-β-N-草酰-α,β-二氨基丙酸（L-β-ODAP）被认为是神经退行性疾病骨软化症的致病因子。我们研究了L-β-ODAP对大鼠脊髓运动神经元中[Ca2+]i处理、氧化还原稳态和细胞死亡的影响。L-β-ODAP和L-谷氨酸引发了[Ca2+]i瞬变，这被α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体阻滞剂所抑制；2,3-二氧代-6-硝基-1,2,3,4-四氢苯并[f]喹喔啉-7-磺酰胺和1-萘基乙酰精胺，后者特异性阻断Ca2+通透的α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体。此外，2,3-二氧代-6-硝基-1,2,3,4-四氢苯并[f]喹喔啉-7-磺酰胺以及程度较轻的1-萘基乙酰精胺保护神经元免受L-β-ODAP或L-谷氨酸诱导的细胞死亡。蛋氨酸和半胱氨酸也对神经元细胞死亡有保护作用。我们得出结论，[Ca2+]i稳态失调和氧化应激导致了骨软化症中运动神经元的细胞死亡。
