Damaging effects of oxygen radicals on resealed erythrocyte ghosts.
Damaging effects of oxygen radicals on resealed erythrocyte ghosts.
复制标题
氧自由基对重新密封的红细胞鬼影的破坏作用。
DOI：
10.1016/s0021-9258(17)43470-3
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发表时间：
1984
期刊：
影响因子：
--
通讯作者：
J. P. Thomas
中科院分区：
文献类型：
--
作者：
A. Girotti;J. P. Thomas
在铁存在的情况下，黄嘌呤氧化酶对黄嘌呤引起的氧化损伤非常敏感。通过脂质过氧化和捕获标记物Na+和葡萄糖-6- p的渗透增加来评估损伤。主要发现如下：(a)黄嘌呤/黄嘌呤氧化酶/铁处理鬼的标志物外排滞后后加速，Na+的出现远远领先于葡萄糖-6- p。(b)铁（III）以剂量依赖的方式刺激外排和脂质过氧化，并被螯合剂抑制。(c)抗氧化剂丁基羟基甲苯有效阻止脂质过氧化和净葡萄糖-6- p外排，但仅部分减缓Na+外排。(d)脂质过氧化和标记物释放均可被超氧化物歧化酶或过氧化氢酶完全抑制，表明O2-和H2O2都是必需的，可能是OH的前体。通过铁催化的Haber-Weiss反应（O2- + H2O2生成OH- + OH）。+ O2)。(e)哦。清除剂，如乙醇、甘露醇、胆碱，对标志物外排和脂质过氧化无保护作用。然而这些药剂确实拦截了OH。因为它们抑制了作为膜外OH添加的2-脱氧核糖的降解。调查。提出OH。在铁结合位点的膜上产生的与目标分子的反应非常迅速，清除剂无法与之竞争。(f)地铁胺消除了所有影响，包括Na+的净排出。EDTA在完全抑制脂质过氧化和葡萄糖-6- p释放的同时，部分减少了Na+的释放，使其变为一级，比背景快约3倍。过氧化氢酶完全抑制后一种反应，而超氧化物歧化酶仅轻微抑制后一种反应。这和其他证据表明，不同形式的膜损伤是导致这两种标志物渗透增强的原因；尽管葡萄糖-6- p依赖于脂质过氧化，但当EDTA存在时，Na+不依赖于脂质过氧化。
Resealed ghosts of human erythrocytes are sensitive to oxidative damage induced by xanthine oxidase acting on xanthine in the presence of iron. Damage was assessed in terms of lipid peroxidation and increased permeation of trapped markers, Na+ and glucose-6-P. Key findings are as follows. (a) Marker efflux from xanthine/xanthine oxidase/iron-treated ghosts accelerated after a lag, Na+ emerging far ahead of glucose-6-P. (b) Both effluxes and lipid peroxidation were stimulated by Fe(III) in a dose-dependent fashion and inhibited by chelating agents. (c) The antioxidant butylated hydroxytoluene effectively halted lipid peroxidation and net glucose-6-P efflux, but slowed Na+ efflux only partially. (d) Lipid peroxidation and marker release could be completely inhibited by superoxide dismutase or catalase, indicating that O2- and H2O2 are both required, possibly as precursors of OH. via the iron-catalyzed Haber-Weiss reaction (O2- + H2O2 leads to OH- + OH. + O2). (e) OH. scavengers, e.g. ethanol, mannitol, choline, had no protective effect against marker efflux and lipid peroxidation. Yet these agents did intercept OH. in the bulk medium, since they inhibited the degradation of 2-deoxyribose added as an extramembranous OH. probe. It is proposed that OH. produced on the membrane at iron binding sites reacts so rapidly with target molecules that scavengers cannot compete. (f) Desferrioxamine abolished all effects, including net egress of Na+. EDTA, while totally inhibitory toward lipid peroxidation and glucose-6-P release, diminished Na+ release partially, changing it to first order, approximately 3-fold faster than background. The latter response was totally inhibited by catalase, but only marginally by superoxide dismutase. This and other evidence suggests that different forms of membrane damage are responsible for enhanced permeation of the two markers; although glucose-6-P depends on lipid peroxidation, Na+ does not, certainly when EDTA is present.