Maher P, Davis J B
Department of Cell Biology, Scripps Research Institute, La Jolla, California 92037, USA.
J Neurosci. 1996 Oct 15;16(20):6394-401. doi: 10.1523/JNEUROSCI.16-20-06394.1996.
Glutamate kills neuronal cells by either a receptor-mediated pathway or the inhibition of cystine uptake, the "oxidative pathway." Antioxidants can block cell death initiated by either pathway, suggesting that toxicity is dependent on the production of free radicals. We provide evidence that in a neuronal cell line, glutamate toxicity via the oxidative pathway requires monoamine metabolism as a source of free radicals. Glutamate toxicity is inhibited by monoamine oxidase (MAO) type-A-specific inhibitors, but only at concentrations much higher than those required to inhibit classical type-A MAO. Toxicity is not inhibited by MAO type-B-specific inhibitors at any concentration. Furthermore, treatment of cells with agents that block monoamine uptake inhibits glutamate toxicity. These results suggest that an enzyme distinct from MAO is involved in monoamine metabolism and demonstrate a relationship between glutamate toxicity and monoamine metabolism. These data also have implications for the understanding and treatment of neurodegenerative disorders in which glutamate toxicity is thought to be involved.
谷氨酸通过受体介导途径或抑制胱氨酸摄取（“氧化途径”）杀死神经元细胞。抗氧化剂可阻断由这两种途径引发的细胞死亡，这表明毒性取决于自由基的产生。我们提供的证据表明，在一种神经元细胞系中，通过氧化途径产生的谷氨酸毒性需要单胺代谢作为自由基的来源。谷氨酸毒性受到A型单胺氧化酶（MAO）特异性抑制剂的抑制，但所需浓度远高于抑制经典A型MAO所需的浓度。MAO B型特异性抑制剂在任何浓度下均不会抑制毒性。此外，用阻断单胺摄取的药物处理细胞可抑制谷氨酸毒性。这些结果表明，一种不同于MAO的酶参与了单胺代谢，并证明了谷氨酸毒性与单胺代谢之间的关系。这些数据对于理解和治疗被认为涉及谷氨酸毒性的神经退行性疾病也具有重要意义。
