Janáky R, Varga V, Hermann A, Saransaari P, Oja S S
Brain Research Center, Medical School, University of Tampere, Finland.
Neurochem Res. 2000 Oct;25(9-10):1397-405. doi: 10.1023/a:1007616817499.
We review here the possible mechanisms of neuronal degeneration caused by L-cysteine, an odd excitotoxin. L-Cysteine lacks the omega carboxyl group required for excitotoxic actions via excitatory amino acid receptors, yet it evokes N-methyl-D-aspartate (NMDA) -like excitotoxic neuronal death and potentiates the Ca2+ influx evoked by NMDA. Both actions are prevented by NMDA antagonists. One target for cysteine effects is thus the NMDA receptor. The following mechanisms are discussed now: (1) possible increase in extracellular glutamate via release or inhibition of uptake/degradation, (2) generation of cysteine alpha-carbamate, a toxic analog of NMDA, (3) generation of toxic oxidized cysteine derivatives, (4) chelation of Zn2+ which blocks the NMDA receptor-ionophore, (5) direct interaction with the NMDA receptor redox site(s), (6) generation of free radicals, and (7) formation of S-nitrosocysteine. In addition to these, we describe another new alternative for cytotoxicity: (8) generation of the neurotoxic catecholamine derivative, 5-S-cysteinyl-3,4-dihydroxyphenylacetate (cysdopac).
我们在此综述由奇特的兴奋性毒素L-半胱氨酸引起神经元变性的可能机制。L-半胱氨酸缺乏通过兴奋性氨基酸受体产生兴奋性毒性作用所需的ω羧基，但它能引发类似N-甲基-D-天冬氨酸（NMDA）的兴奋性毒性神经元死亡，并增强NMDA诱发的Ca2+内流。这两种作用均能被NMDA拮抗剂阻断。因此，半胱氨酸作用的一个靶点是NMDA受体。现将以下机制进行讨论：（1）通过释放或抑制摄取/降解可能导致细胞外谷氨酸增加；（2）生成半胱氨酸α-氨基甲酸酯，一种NMDA的毒性类似物；（3）生成有毒的氧化半胱氨酸衍生物；（4）螯合Zn2+，其可阻断NMDA受体离子通道；（5）与NMDA受体氧化还原位点直接相互作用；（6）产生自由基；（7）形成S-亚硝基半胱氨酸。除此之外，我们还描述了另一种细胞毒性的新机制：（8）生成神经毒性儿茶酚胺衍生物5-S-半胱氨酰-3,4-二羟基苯乙酸（cysdopac）。
