Michikawa M, Lim K T, McLarnon J G, Kim S U
Department of Medicine, University of British Columbia, Vancouver, Canada.
J Neurosci Res. 1994 Jan;37(1):62-70. doi: 10.1002/jnr.490370109.
The neurotoxic effects of oxygen radicals on spinal cord neuron cultures derived from fetal mouse have been studied. Oxygen radicals, superoxide radical and hydrogen peroxide, were generated by adding xanthine oxidase and hypoxanthine in the culture medium. Exposure of neurons to this oxygen radical-generating system resulted in a significant cell death and decrease of choline acetyltransferase (ChAT) activity in a time-dependent manner in spinal cord neuron cultures. The decrease in cell viability and ChAT enzyme activity induced by the oxygen radicals was blocked by scavengers such as superoxide dismutase (SOD), catalase, and tetrakis (2-pyridylmethyl) ethylenediamine (TPEN), a metal chelator. Antagonists of the N-methyl-D-aspartate (NMDA) receptor, including MK801 (a noncompetitive NMDA antagonist), D-2-amino-5-phosphonovaleric acid (APV) (a competitive NMDA antagonist), and 7-chlorokynurenic acid (an antagonist at the glycine site associated with the NMDA receptor), similarly blocked oxygen radical-induced decrease in cell viability and ChAT activity in spinal cord neuron cultures. These results indicate that both oxygen radicals and excitotoxic amino acids were involved in the oxidant-initiated neurotoxicity of spinal cord neurons.
已经对氧自由基对源自胎鼠的脊髓神经元培养物的神经毒性作用进行了研究。通过在培养基中添加黄嘌呤氧化酶和次黄嘌呤来产生氧自由基、超氧阴离子自由基和过氧化氢。将神经元暴露于这种产氧自由基系统会导致脊髓神经元培养物中细胞显著死亡，并使胆碱乙酰转移酶（ChAT）活性呈时间依赖性降低。氧自由基诱导的细胞活力和ChAT酶活性的降低被超氧化物歧化酶（SOD）、过氧化氢酶和金属螯合剂四（2-吡啶甲基）乙二胺（TPEN）等清除剂所阻断。N-甲基-D-天冬氨酸（NMDA）受体拮抗剂，包括MK801（一种非竞争性NMDA拮抗剂）、D-2-氨基-5-磷酸戊酸（APV）（一种竞争性NMDA拮抗剂）和7-氯犬尿氨酸（一种与NMDA受体相关的甘氨酸位点拮抗剂），同样阻断了氧自由基诱导的脊髓神经元培养物中细胞活力和ChAT活性的降低。这些结果表明，氧自由基和兴奋性毒性氨基酸都参与了脊髓神经元的氧化引发的神经毒性。
