Why does SOD overexpression sometimes enhance, sometimes decrease, hydrogen peroxide production? A minimalist explanation
Why does SOD overexpression sometimes enhance, sometimes decrease, hydrogen peroxide production? A minimalist explanation
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DOI：
10.1016/s0891-5849(02)00861-4
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发表时间：
2002-06-15
影响因子：
7.4
通讯作者：
Moradas-Ferreira, P
中科院分区：
文献类型：
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作者：
Gardner, R;Salvador, A;Moradas-Ferreira, P
超氧化物歧化酶（SOD）过表达的毒性作用通常归因于过氧化氢（H2O2）产生的增加。然而，关于SOD过表达是否会增加或减少H2O2的产生，已发表的实验得出了相互矛盾的证据。我们使用最小数学模型分析了这个问题。超氧化物消耗的最相关机制被视为伪一级过程，超氧化物的产生和SOD以外的酶的活性都被认为是恒定的。即使在这个简单的框架内，SOD过表达也可能增加、保持不变或减少H2O2的产生。在正常的SOD水平下，结果取决于消耗超氧化物而不生成H2O2的过程速率与消耗超氧化物而产生高（大于或等于1）H2O2的过程速率之间的比率。在这个比例非常低的细胞或细胞室中（< 1），预计SOD过表达后H2O2的产生会适度减少。当比值大于1时，H2O2产量随着SOD活性的增加而增加，但几乎呈线性增长。所得结果与已有的实验观测结果一致。根据最小模型，在一些实验中，只有当大部分超氧化物通过无H2O2的过程被消除时，SOD活性才会对H2O2的产生产生中等程度的影响。(C) 2002爱思唯尔科学有限公司
Toxic effects of superoxide dismutase (SOD) overexpression are commonly attributed to increased hydrogen peroxide (H2O2) production. Still, published experiments yield contradictory evidence on whether SOD overexpression increases or decreases H2O2 production. We analyzed this issue using a minimal mathematical model. The most relevant mechanisms of superoxide consumption are treated as pseudo first-order processes, and both superoxide production and the activity of enzymes other than SOD were considered constant. Even within this simple framework, SOD overexpression may increase, hold constant, or decrease H2O2 production. At normal SOD levels, the outcome depends on the ratio between the rate of processes that consume superoxide without forming H2O2 and the rate of processes that consume superoxide with high (greater than or equal to 1) H2O2 yield. In cells or cellular compartments where this ratio is exceptionally low (< 1), a modest decrease in H2O2 production upon SOD overexpression is expected. Where the ratio is higher than unity, H2O2 production should increase, but at most linearly, with SOD activity. The results are consistent with the available experimental observations. According to the minimal model, only where most superoxide is eliminated through H2O2-free processes does SOD activity have the moderately large influence on H2O2 production observed in some experiments. (C) 2002 Elsevier Science Inc.