Sources for superoxide release: lessons from blockade of electron transport, NADPH oxidase, and anion channels in diaphragm.
Sources for superoxide release: lessons from blockade of electron transport, NADPH oxidase, and anion channels in diaphragm.
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超氧化物释放的来源：电子传输、NADPH 氧化酶和隔膜阴离子通道阻断的教训。
DOI：
10.1089/152308603770310347
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发表时间：
2003
影响因子：
6.6
通讯作者：
Clanton,ThomasL
中科院分区：
文献类型：
--
作者：
Zuo,Li;Pasniciuc,Silviu;Wright,ValerieP;Merola,AJohn;Clanton,ThomasL
隔离隔膜在静止时释放低水平的超氧化物(O2·-)，在热应激时释放高得多的超氧阴离子。分子来源尚不清楚。这一假设得到了检验，即热应激刺激线粒体复合体活性或NADPH氧化酶，导致O2·-释放增加。复合体I(异巴比妥钠或鱼藤酮)或复合体I和II(鱼藤酮+噻吩甲酰三氟丙酮)对完整大鼠膈肌线粒体有抑制作用。二苯基碘对NADPH氧化酶有抑制作用。这些处理均不能抑制O2·-的释放。相反，大多数阻滞剂都能刺激O2·-的释放。由于细胞内O2·-的产生需要一种跨膜转运O2·-的机制，因此也对阴离子通道阻滞剂丙磺舒和4，4‘-diisothiocyanato-stilbene-2，2’-disulfonic酸进行了测试。两种阻断剂对O2·-释放均无抑制作用。这些结果表明，隔膜释放的O2·-不直接依赖于线粒体复合体的活性，也不是O2·-通过阴离子通道被动扩散的反映。尽管细胞外O2·-的分子来源尚不清楚，但它显然对温度和部分或完全线粒体抑制引起的“化学缺氧”条件很敏感。
Isolated diaphragm releases low levels of superoxide (O2•-) at rest and much higher levels during heat stress. The molecular source is unknown. The hypothesis was tested that heat stress stimulates mitochondrial complex activity or NADPH oxidases, resulting in increased O2•-release. The mitochondria within intact rat diaphragm were inhibited at complex I (amobarbital or rotenone) or complex I and II (rotenone plus thenoyltrifluoroacetone). NADPH oxidases were blocked by diphenyliodonium. None of these treatments inhibited O2•-release. Conversely, most blockers stimulated O2•-release. As intracellular O2•-generators require a mechanism for O2•-transport across the membrane, anion channel blockers, probenecid and 4,4'-diisothiocyanato-stilbene-2,2'-disulfonic acid, were also tested. Neither blocker had any inhibitory effect on O2•-release. These results suggest that O2•-released from diaphragm is not directly dependent on mitochondrial complex activity and that it is not a reflection of passive diffusion of O2•-through anion channels. Although the molecular source for extracellular O2•-remains elusive, it is clearly sensitive to temperature and conditions of "chemical hypoxia" induced by partial or complete mitochondrial inhibition.