Kikuchi M, Kashii S, Honda Y, Tamura Y, Kaneda K, Akaike A
Department of Ophthalmology, Graduate School of Medicine, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Invest Ophthalmol Vis Sci. 1997 Apr;38(5):848-54.
To examine the effects of methylcobalamin on glutamate-induced neurotoxicity in the cultured retinal neurons.
Primary cultures obtained from the fetal rat retina (gestation days 16 to 19) were used for the experiment. The neurotoxicity was assessed quantitatively using the trypan blue exclusion method.
Glutamate neurotoxicity was prevented by chronic exposure to methylcobalamin and S-adenosylmethionine (SAM), which is formed in the metabolic pathway of methylcobalamin. Chronic exposure to methylcobalamin and SAM also inhibited the neurotoxicity induced by sodium nitroprusside that release nitric oxide. By contrast, acute exposure to methylcobalamin did not protect retinal neurons against glutamate neurotoxicity.
Chronic administration of methylcobalamin protects cultured retinal neurons against N-methyl-D-aspartate-receptor-mediated glutamate neurotoxicity, probably by altering the membrane properties through SAM-mediated methylation.
研究甲钴胺对培养的视网膜神经元中谷氨酸诱导的神经毒性的影响。
实验采用从胎鼠视网膜(妊娠第16至19天)获得的原代培养物。使用台盼蓝排斥法对神经毒性进行定量评估。
长期暴露于甲钴胺和S-腺苷甲硫氨酸(SAM,在甲钴胺的代谢途径中形成)可预防谷氨酸神经毒性。长期暴露于甲钴胺和SAM还可抑制由释放一氧化氮的硝普钠诱导的神经毒性。相比之下,急性暴露于甲钴胺并不能保护视网膜神经元免受谷氨酸神经毒性的影响。
长期给予甲钴胺可保护培养的视网膜神经元免受N-甲基-D-天冬氨酸受体介导的谷氨酸神经毒性,可能是通过SAM介导的甲基化改变膜特性来实现的。