OXIDATIVE DAMAGE TO BRAIN PROTEINS, LOSS OF GLUTAMINE-SYNTHETASE ACTIVITY, AND PRODUCTION OF FREE-RADICALS DURING ISCHEMIA REPERFUSION-INDUCED INJURY TO GERBIL BRAIN
OXIDATIVE DAMAGE TO BRAIN PROTEINS, LOSS OF GLUTAMINE-SYNTHETASE ACTIVITY, AND PRODUCTION OF FREE-RADICALS DURING ISCHEMIA REPERFUSION-INDUCED INJURY TO GERBIL BRAIN
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DOI：
10.1073/pnas.87.13.5144
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发表时间：
1990-07-01
影响因子：
11.1
通讯作者：
FLOYD, RA
中科院分区：
文献类型：
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作者：
OLIVER, CN;STARKEREED, PE;FLOYD, RA
自由基介导的氧化损伤与缺血/再灌注事件引起的组织损伤有关。蒙古沙鼠脑皮质缺血再灌注损伤是由双颈总动脉短暂闭塞引起的。以蛋白质羰基含量测定的蛋白质氧化在缺血10 min后的再灌注阶段显著增加。谷氨酰胺合成酶（一种已知被金属催化氧化反应失活的酶）的活性在缺血10分钟后再灌注2小时后下降到对照水平的65%。我们还报道了自由基自旋阱n -叔丁基-。-苯硝酮[300 mg/kg（体重）]在缺血/再灌注开始前60分钟给予，部分防止蛋白质氧化和保护谷氨酰胺合成酶活性的丧失。此外，我们还报道了一个n -叔丁基。在缺血/再灌注损伤脑的脂质部分中获得-苯基硝基依赖的氮氧化物自由基，但在类似的假手术对照脑中存在很少的自由基。这些数据加强了先前使用体内捕获方法的观察结果，即在缺血损伤的沙鼠脑的再灌注阶段自由基通量增加。谷氨酰胺合成酶的丧失预计会增加大脑中l -谷氨酸的水平。因此，谷氨酰胺合成酶的氧化失活可能是脑缺血再灌注损伤后产生神经毒性的关键因素。
Free radical-mediated oxidative damage has been implicated in tissue injury resulting from ischemia/reperfusion events. Global cortical ischemia/reperfusion injury to Mongolian gerbil brains was produced by transient occlusion of both common carotid arteries. Protein oxidation, as measured by protein carbonyl content, increased significantly during the reperfusion phase that followed 10 min of ischemia. The activity of glutamine synthetase, an enzyme known to be inactivated by metal-catalyzed oxidation reactions, decreased to 65% of control levels after 2 hr of reperfusion that followed 10 min of ischemia. We also report that the free radical spin trap N-tert-butyl-.alpha.-phenylnitrone [300 mg/kg (body weight)] administered 60 min before ischemia/reperfusion is initiated, partially prevents protein oxidation and protects from loss of glutamine synthetase activity. In addition, we report a N-tert-butyl-.alpha.-phenylnitrone-dependent nitroxide radical obtained in the lipid fraction of the ischemia/reperfusion-lesioned brains, but there was very little radical present in the comparable sham-operated control brains. These data strenthen the previous observation utilizing in vivo-trapping methods, that free radical flux is increased during the reperfusion phase of the ischemia-lesioned gerbil brain. The loss of glutamine synthetase would be expected to increase the levels of brain L-glutamate. Thus, the oxidative inactivation of glutamine synthetase may be a critical factor in the neurotoxicity produced after cerebral ischemia/reperfusion injury.