In vitro effect of the cysteine metabolites homocysteic acid, homocysteine and cysteic acid upon human neuronal cell lines.
In vitro effect of the cysteine metabolites homocysteic acid, homocysteine and cysteic acid upon human neuronal cell lines.
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发表时间：
1998-08
期刊：
影响因子：
3.4
通讯作者：
R. Parsons;R. Waring;D. Ramsden;A. Williams
中科院分区：
文献类型：
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作者：
R. Parsons;R. Waring;D. Ramsden;A. Williams
半胱氨酸 (CYS) 是一种非必需氨基酸，通过谷氨酸受体的 N-甲基-D-天冬氨酸 (NMDA) 亚型引发兴奋毒性。已知 CYS 水平升高与阿尔茨海默病 (AD) 和帕金森病 (PD) 等神经系统疾病有关。我们之前报道过研究 CYS 及其主要代谢物半胱亚磺酸 (CSA) 对人类神经元细胞系的体外毒性，现在我们报道了 CYS 代谢途径中其他化合物（同型半胱氨酸，HCA；同型半胱氨酸，HCYS；和半胱氨酸，CA）的毒性。神经毒性测定中使用了三种细胞系，全部来自人类并源自大脑的不同离散区域。测定乳酸脱氢酶（LDH）释放作为细胞死亡的量度。所研究的细胞系表现出不同程度的毒性反应，这与暴露于 CYS 或 CSA 时所观察到的毒性反应相反。 SK.N.SH（神经母细胞瘤）细胞系对 CYS 和 CSA 表现出高毒性反应，对 HCA 和 CA 表现出低毒性反应，而 TE 671（成神经管细胞瘤）细胞系对 CYS 和 CSA 表现出低毒性反应，但对 HCYS、HCA 和 CA 表现出高毒性反应。然而，U-87 MG（胶质母细胞瘤）细胞系对 CYS 和 CSA 具有中等毒性反应，对 HCYS、HCA 和 CA 也具有中等毒性反应。这些结果表明，CYS 及其代谢物的毒性反应是细胞类型特异性的，这可能反映在 AD 和 PD 等疾病中观察到的神经变性模式中。 HCYS对髓母细胞瘤细胞具有选择性毒性；这可以解释为什么高 HCYS 水平会导致产前人类神经管缺陷，其中涉及相同的细胞类型。
Cysteine (CYS) is a non-essential amino acid which elicits excitotoxic properties via the N-methyl-D-aspartate (NMDA) subtype of the glutamate receptor. CYS levels are known to be elevated in association with neurological disease such as Alzheimers Disease (AD) and Parkinsons Disease (PD). We have previously reported studies investigating the toxicity of CYS and its major metabolite cysteinesulfinic acid (CSA) to human neuronal cell lines in vitro and in continuation of this we now report the toxicity of other compounds (Homocysteic Acid, HCA; Homocysteine, HCYS; and Cysteic Acid, CA) in the CYS metabolic pathway. Three cell lines, all of human origin and derived from separate discrete areas of the brain were used in the neurotoxicity assays. Lactate dehydrogenase (LDH) release was assayed as a measure of cell death. The cell lines investigated showed varying degrees of toxic responses which were the reverse of those seen when they were exposed to CYS or CSA. The SK.N.SH (Neuroblastoma) cell line, which exhibits a high toxic response to CYS and CSA, gave a low toxic response to HCA and CA while the TE 671 (Medulloblastoma) cell line, which exhibits a low toxic response to CYS and CSA, showed a high toxic response to HCYS, HCA and CA. However, the U-87 MG (Glioblastoma) cell line, which has a median toxic response to CYS and CSA, also has median response to HCYS, HCA and CA. These results show that toxic responses are cell-type specific for CYS and its metabolites and this may be reflected in the patterns of neurodegeneration observed in such diseases as AD and PD. HCYS is selectively toxic to medulloblastoma cells; this may explain why high HCYS levels result in neural tube defects in prenatal humans, where the same cell-type is involved.