Regulation of xanthine oxidoreductase by intracellular iron
Regulation of xanthine oxidoreductase by intracellular iron
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DOI：
10.1152/ajpcell.00280.2002
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发表时间：
2002-12-01
影响因子：
5.5
通讯作者：
Raivio, KO
中科院分区：
文献类型：
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作者：
Martelin, E;Lapatto, R;Raivio, KO
黄嘌呤氧化还原酶（XOR）可产生活性氧，在缺血再灌注损伤中发挥作用。由于缺血后组织铁水平增加，并且由于XOR含有功能关键的铁硫簇，我们研究了细胞内铁对XOR表达的影响。柠檬酸铁铵和FeSO 4提高细胞内铁水平，并增加XOR活动在小鼠成纤维细胞和人支气管上皮细胞的两倍。铁增加XOR蛋白质和mRNA水平，而蛋白质和RNA合成抑制剂取消了XOR活性的诱导。人XOR启动子构建体（核苷酸+42至-1937）在人胚肾细胞中不被铁诱导。羟自由基清除剂并没有阻止铁的异或反应活性的诱导。铁螯合去铁胺（DFO）降低XOR活性，但不降低内源性XOR蛋白或mRNA水平。此外，DFO降低过表达的人XOR的活性，但不减少免疫反应蛋白的量。我们的数据表明，XOR活动是转录诱导铁，但postperitonally铁螯合失活。
Xanthine oxidoreductase (XOR) may produce reactive oxygen species and play a role in ischemia-reperfusion injury. Because tissue iron levels increase after ischemia, and because XOR contains functionally critical iron-sulfur clusters, we studied the effects of intracellular iron on XOR expression. Ferric ammonium citrate and FeSO4 elevated intracellular iron levels and increased XOR activity up to twofold in mouse fibroblast and human bronchial epithelial cells. Iron increased XOR protein and mRNA levels, whereas protein and RNA synthesis inhibitors abolished the induction of XOR activity. A human XOR promoter construct (nucleotides +42 to -1937) was not induced by iron in human embryonic kidney cells. Hydroxyl radical scavengers did not block induction of XOR activity by iron. Iron chelation by deferoxamine (DFO) decreased XOR activity but did not lower endogenous XOR protein or mRNA levels. Furthermore, DFO reduced the activity of overexpressed human XOR but not the amount of immunoreactive protein. Our data show that XOR activity is transcriptionally induced by iron but posttranslationally inactivated by iron chelation.