Scott M D, Eaton J W, Kuypers F A, Chiu D T, Lubin B H
Children's Hospital Oakland Research Institute, CA 94609.
Blood. 1989 Nov 15;74(7):2542-9.
To delineate further the role of superoxide dismutase (SOD) in red blood cell (RBC) oxidant defense, normal human erythrocytes were osmotically lysed and resealed in the presence of varying concentrations of exogenous SOD. This resulted in a dose-dependent increase in SOD activity in the resealed erythrocytes while maintaining nearly normal RBC hemoglobin concentration (less than 10% decrease from the control value), cell volume, and cellular deformability. Surprisingly, a five- or ninefold increase in SOD activity yielded no additional protection against superoxide-generating drugs (phenazine methosulfate or menadione sodium bisulfite). No significant differences were observed between the control and SOD-loaded RBCs in O2-driven methemoglobin formation or generation of thiobarbituric acid-reactive substances. In contrast, RBCs with elevated SOD activity pretreated with sodium azide (to block catalase activity) or 1-chloro-2,4-dinitrobenzene (to deplete reduced glutathione, GSH) showed significantly enhanced methemoglobin generation in response to superoxide generating drugs. No differential response was noted between the control, control-resealed, and SOD-loaded RBCs to oxidants other than superoxide. Based on our results and other data, we conclude that elevated SOD activity may imbalance cellular oxidant defense, resulting in enhanced oxidation due to the accelerated generation of H2O2, the product of O2- dismutation. This effect is significantly exacerbated under conditions in which H2O2 catabolism is altered.
为了进一步阐明超氧化物歧化酶（SOD）在红细胞（RBC）抗氧化防御中的作用，将正常人红细胞进行渗透裂解，并在不同浓度的外源性SOD存在下重新封闭。这导致重新封闭的红细胞中SOD活性呈剂量依赖性增加，同时保持红细胞血红蛋白浓度接近正常（比对照值降低不到10%）、细胞体积和细胞变形性。令人惊讶的是，SOD活性增加五倍或九倍并不能提供额外的保护，以抵抗产生超氧化物的药物（硫酸吩嗪或亚硫酸氢钠甲萘醌）。在氧气驱动的高铁血红蛋白形成或硫代巴比妥酸反应性物质的产生方面，对照红细胞和加载SOD的红细胞之间未观察到显著差异。相比之下，用叠氮化钠预处理（以阻断过氧化氢酶活性）或1-氯-2,4-二硝基苯（以耗尽还原型谷胱甘肽，GSH）使SOD活性升高的红细胞，在对产生超氧化物的药物的反应中，高铁血红蛋白的生成显著增强。对照红细胞、对照重新封闭的红细胞和加载SOD的红细胞对除超氧化物以外的氧化剂没有差异反应。根据我们的结果和其他数据，我们得出结论，升高的SOD活性可能会使细胞抗氧化防御失衡，由于超氧阴离子歧化产物H2O2的加速生成而导致氧化增强。在H2O2分解代谢改变的条件下，这种效应会显著加剧。
