Expression of the hydrogen peroxide-generating enzyme fatty acyl CoA oxidase activates NF-kappaB.
Expression of the hydrogen peroxide-generating enzyme fatty acyl CoA oxidase activates NF-kappaB.
复制标题
过氧化氢生成酶脂肪酰辅酶 A 氧化酶的表达会激活 NF-κB。
DOI：
10.1089/104454900314627
复制
发表时间：
2000
影响因子：
3.1
通讯作者：
Spear,BT
中科院分区：
文献类型：
--
作者：
Li,Y;Tharappel,JC;Cooper,S;Glenn,M;Glauert,HP;Spear,BT
过氧化物酶体增殖物是一类啮齿动物的肝脏致癌物，已被认为部分是通过增加氧化应激来发挥作用的。脂肪酰辅酶A氧化酶(FAO)是过氧化物酶体内β-氧化途径中的过氧化氢产生酶，由过氧化物体增殖物高度诱导。我们先前的研究表明，用过氧化物酶增殖剂环丙贝特处理大鼠和小鼠后，肝脏的核因子-kappaB活性增加，提示这种作用可能是过氧化氢产生酶的次要作用。为了直接测试这种可能性，我们已经确定了在没有过氧化物酶体增殖物的情况下，FAO的瞬时过表达是否会导致NF-kappa B的激活。在这里，我们证明了FAO在Cos-1细胞中的过表达，在存在过氧化氢产生底物的情况下，可以激活NF-kappa B调节的报告基因。电泳迁移率改变分析进一步表明，FAO的表达以一种剂量依赖的方式增加了核NF-kappa B DNA结合活性。抗氧化剂维生素E和过氧化氢酶可以抑制这种激活。这些结果表明，粮农组织至少部分地介导了过氧化物酶体增殖物诱导的核因子-kappaB的激活。
Peroxisome proliferators are a class of hepatic carcinogens in rodents and have been proposed to act in part by increasing oxidative stress. Fatty acyl CoA oxidase (FAO), which is highly induced by peroxisome proliferators, is the hydrogen peroxide-generating enzyme of the peroxisomal beta-oxidation pathway. We previously showed that the treatment of rats and mice with the peroxisome proliferator ciprofibrate resulted in increased hepatic NF-kappa B activity and suggested that this effect may be secondary to the action of H2O2-generating enzymes. To test this possibility directly, we have determined whether transient overexpression of FAO, in the absence of peroxisome proliferators, leads to NF-kappa B activation. Here, we show that FAO overexpression in Cos-1 cells, in the presence of an H2O2-generating substrate, can activate a NF-kappa B regulated reporter gene. Electrophoretic mobility shift assays further demonstrated that FAO expression increases nuclear NF-kappa B DNA binding activity in a dose-dependent manner. The antioxidants vitamin E and catalase can inhibit this activation. These results indicate that FAO mediates, at least in part, peroxisome proliferator-induced NF-kappa B activation.