Oxidation of 2-Cys-peroxiredoxins by arachidonic acid peroxide metabolites of lipoxygenases and cyclooxygenase-2
Oxidation of 2-Cys-peroxiredoxins by arachidonic acid peroxide metabolites of lipoxygenases and cyclooxygenase-2
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DOI：
10.1074/jbc.m704369200
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发表时间：
2007-11-09
影响因子：
4.8
通讯作者：
Fitzpatrick, Frank A.
中科院分区：
文献类型：
--
作者：
Cordray, Pauline;Doyle, Kelly;Fitzpatrick, Frank A.
人的过氧化还蛋白具有抗氧化剂和调节过氧化氢介导的细胞信号的双重作用。过氧化还蛋白的功能多样性依赖于关键半胱氨酸残基的逐步氧化。亚磺酸或磺酸形式的过氧化氢还蛋白失去了过氧化物酶活性，这使得细胞积累了过氧化氢，用于炎症、癌症和其他疾病中的信号或发病机制。我们报道了5-，12-，15-脂氧合酶-1和环氧合酶-2的花生四烯酸脂过氧化氢代谢产物将2-环氧还蛋白1，2和3氧化成亚磺酸和磺酸形式。当外源添加到细胞中时，5-、12-和15-羟基过氧二十碳四烯酸也会过度氧化过氧化还蛋白。我们的结果表明，脂肪氧合酶和环氧合酶可能影响2-半胱氨酸过氧化还蛋白信号，类似于“闸门”模型中的NADPH氧化酶(Wood，Z.A.，Poole，L.B，and Karplus P.A.(2003)Science 300,600-653)。过氧化还蛋白依赖的机制可能调节细胞脂氧合酶和环氧合酶催化产生的自糖皮质激素的受体依赖行为。
Human peroxiredoxins serve dual roles as anti- oxidants and regulators of H2O2- mediated cell signaling. The functional versatility of peroxiredoxins depends on progressive oxidation of key cysteine residues. The sulfinic or sulfonic forms of peroxiredoxin lose their peroxidase activity, which allows cells to accumulate H2O2 for signaling or pathogenesis in inflammation, cancer, and other disorders. We report that arachidonic acid lipid hydroperoxide metabolites of 5-, 12-, 15- lipoxygenase- 1, and cyclooxygenase- 2 oxidize the 2- Cysperoxiredoxins 1, 2, and 3 to their sulfinic and sulfonic forms. When added exogenously to cells, 5-, 12- and 15- hydroperoxyeicosatetraenoic acids also over- oxidized peroxiredoxins. Our results suggest that lipoxygenases and cyclooxygenases may affect 2- Cys peroxiredoxin signaling, analogous to NADPH oxidases in the " floodgate" model ( Wood, Z. A., Poole, L. B, and Karplus P. A. ( 2003) Science 300, 600 - 653). Peroxiredoxin- dependent mechanisms may modulate the receptor- dependent actions of autocoids derived from cellular lipoxygenase and cyclooxygenase catalysis.