L-pyroglutamic acid protects rat cortical neurons against sodium glutamate-induced injury.

X Q Xiao, G Q Liu
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Abstract

Aim: To evaluate the effects of L-pyroglutamic acid (L-PGA, L-5-oxo-2-pyrrolidinecaroxylic acid) on sodium glutamate-induced neurotoxicity in rat cortical neurons.

Methods: In primary cortical cultures from 16-d-old fetal rat, neuronal viability and contents of nitrite in the bathing medium after transient exposure to sodium glutamate (Glu) were measured; with Fura 2-AM as an intracellular calcium indicator, AR-CM-MIC cation measurement system was used to examine cytosolic free calcium ([Ca2+]i).

Results: L-PGA 10-80 mumol.L-1, inhibited Glu (500 mumol.L-1)-induced neuronal loss in a concentration-dependent manner with IC50 value of (41 +/- 9) mumol.L-1 (95% confidence limits: 30.3-54.7 mumol.L-1). L-PGA also attenuated Glu-induced NO release. L-PGA 1, 3, 10, 30, and 100 mumol.L-1 depressed Glu-caused [Ca2+]i elevation by 20.5%, 34.4%, 47.7%, 70.6%, and 80.4%, respectively.

Conclusion: L-PGA protects cortical neurons against Glu-induced neurotoxity which may be related to inhibition of NO formation or suppression of the rise in [Ca2+]i.

l -焦谷氨酸保护大鼠皮层神经元免受谷氨酸钠诱导的损伤。
目的:探讨l -焦谷氨酸(L-PGA, l -5-氧-2-吡咯烷甲酸)对谷氨酸钠诱导的大鼠皮质神经元神经毒性的影响。方法:测定16 d龄胎鼠皮层原代培养物短暂暴露于谷氨酸钠(Glu)后,沐浴液中神经元活力和亚硝酸盐含量;以Fura 2-AM为胞内钙离子指示剂,采用AR-CM-MIC阳离子测量系统检测胞内游离钙([Ca2+]i)。结果:L-PGA 10 ~ 80 μ mol。L-1抑制Glu (500 μ mol.L-1)诱导的神经元损失,IC50值为(41 +/- 9)μ mol。L-1(95%置信限:30.3-54.7 mmol .L-1)。L-PGA也能减弱葡萄糖诱导的NO释放。L-PGA 1,3,10,30和100 μ mol。L-1抑制的glu引起的[Ca2+]i升高分别为20.5%、34.4%、47.7%、70.6%和80.4%。结论:L-PGA可保护皮质神经元免受glu诱导的神经毒性,其机制可能与抑制NO形成或抑制[Ca2+]i升高有关。
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