Scott M D, Meshnick S R, Eaton J W
J Biol Chem. 1987 Mar 15;262(8):3640-5.
Superoxide dismutase is considered important in protection of aerobes against oxidant damage, and increased tolerance to oxidant stress is associated with induction of this enzyme. However, the importance of superoxide dismutase in this tolerance is not clear because conditions which promote the synthesis of superoxide dismutase likewise affect other antioxidant enzymes and substances. To clarify the role of superoxide dismutase per se in organismal defense against oxidant-generating drugs, we employed Escherichia coli transformed with multiple copies of the gene for bacterial iron superoxide dismutase. These bacteria have greater than ten times the superoxide dismutase activity of wild-type E. coli but, importantly, are normal in other oxidant defense parameters including catalase, peroxidases, glutathione, and glutathione reductase. High superoxide dismutase and control bacteria were exposed to the O2- -generating drug paraquat and to elevated pO2. We find; high superoxide dismutase E. coli are more readily killed by paraquat under aerobic, but not anaerobic, conditions. During exposure to paraquat, high superoxide dismutase E. coli accumulate more H2O2. Coincidentally, the reduced glutathione content of high superoxide dismutase E. coli declines more than in control E. coli. E. coli with high superoxide dismutase activity are also more readily killed by hyperoxia. Interestingly, the susceptibility of the parental and high superoxide dismutase E. coli to killing by exogenous H2O2 is not significantly different. Thus, under these experimental conditions, greatly enhanced superoxide dismutase activity accelerates H2O2 formation. The increased H2O2 probably accounts for the exaggerated sensitivity of high superoxide dismutase bacteria to oxidant-generating drugs. These results support the concept that the product of superoxide dismutase, H2O2, is at least as hazardous as the substrate, O2-. We conclude that effective organismal defense against reactive oxygen species may require balanced increments in antioxidant enzymes and cannot necessarily be improved by increases in the activity of single enzymes.
超氧化物歧化酶被认为在保护需氧生物免受氧化损伤方面很重要，对氧化应激耐受性的提高与该酶的诱导有关。然而，超氧化物歧化酶在这种耐受性中的重要性尚不清楚，因为促进超氧化物歧化酶合成的条件同样会影响其他抗氧化酶和物质。为了阐明超氧化物歧化酶本身在生物体抵御产生氧化剂的药物中的作用，我们使用了用细菌铁超氧化物歧化酶基因的多个拷贝转化的大肠杆菌。这些细菌的超氧化物歧化酶活性比野生型大肠杆菌高十倍以上，但重要的是，它们在包括过氧化氢酶、过氧化物酶、谷胱甘肽和谷胱甘肽还原酶在内的其他氧化防御参数方面是正常的。将高表达超氧化物歧化酶的细菌和对照细菌暴露于产生O2-的药物百草枯和升高的pO2环境中。我们发现，在有氧但非厌氧条件下，高表达超氧化物歧化酶的大肠杆菌更容易被百草枯杀死。在接触百草枯期间，高表达超氧化物歧化酶的大肠杆菌积累更多的H2O2。巧合的是，高表达超氧化物歧化酶的大肠杆菌中还原型谷胱甘肽的含量下降幅度比对照大肠杆菌更大。超氧化物歧化酶活性高的大肠杆菌也更容易被高氧杀死。有趣的是，亲本大肠杆菌和高表达超氧化物歧化酶的大肠杆菌对外源H2O2杀伤的敏感性没有显著差异。因此，在这些实验条件下，超氧化物歧化酶活性的大幅增强会加速H2O2的形成。增加的H2O2可能是高表达超氧化物歧化酶的细菌对产生氧化剂的药物过度敏感的原因。这些结果支持了这样一种观点，即超氧化物歧化酶的产物H2O2至少与底物O2-一样具有危害性。我们得出结论，生物体对活性氧的有效防御可能需要抗氧化酶的平衡增加，而不能仅仅通过单一酶活性的增加来改善。
