Kim W K, Pae Y S
Department of Pharmacology, College of Medicine, Ewha Womans University, Seoul, South Korea.
Neurosci Lett. 1996 Sep 27;216(2):117-20. doi: 10.1016/0304-3940(96)13011-1.
The present study investigates the possible mechanism responsible for the neurotoxicity of D,L-homocysteine in primary culture of rat cerebellar granule cells. Neurotoxicity was assessed by measuring the amount of lactate dehydrogenase released from the cells following homocysteine treatment. D,L-Homocysteine (> 300 microM; 16-22 h) induced the release of lactate dehydrogenase from the cells in a concentration-dependent manner. The N-methyl-D-aspartate (NMDA) antagonist (+/-)-2-amino-5-phosphonopentanoic acid (APV) partially blocked the homocysteine-mediated neurotoxicity. However, the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) did not block the homocysteine-mediated toxicity. The homocysteine-mediated neurotoxicity was mostly prevented by the co-administration of superoxide dismutase and catalase or catalase alone. The results suggest that homocysteine induces neuronal cell death by stimulating NMDA receptor as well as by producing free radicals.
本研究探讨了D，L-同型半胱氨酸在大鼠小脑颗粒细胞原代培养中引起神经毒性的可能机制。通过测量同型半胱氨酸处理后细胞释放的乳酸脱氢酶量来评估神经毒性。D，L-同型半胱氨酸（> 300 microM；16 - 22小时）以浓度依赖的方式诱导细胞释放乳酸脱氢酶。N-甲基-D-天冬氨酸（NMDA）拮抗剂（±）-2-氨基-5-膦酰基戊酸（APV）部分阻断了同型半胱氨酸介导的神经毒性。然而，非NMDA受体拮抗剂6-氰基-7-硝基喹喔啉-2,3-二酮（CNQX）并未阻断同型半胱氨酸介导的毒性。同型半胱氨酸介导的神经毒性在同时给予超氧化物歧化酶和过氧化氢酶或仅给予过氧化氢酶时大多可被预防。结果表明，同型半胱氨酸通过刺激NMDA受体以及产生自由基来诱导神经元细胞死亡。
