Rao G N, Glasgow W C, Eling T E, Runge M S
Division of Cardiology, University of Texas Medical Branch, Galveston, Texas 77555, USA.
J Biol Chem. 1996 Nov 1;271(44):27760-4. doi: 10.1074/jbc.271.44.27760.
We have previously reported that hydrogen peroxide, an active oxygen species and a cellular oxidant, induces c-Fos and c-Jun mRNA expression and DNA synthesis in vascular smooth muscle cells and that these events require arachidonic acid release and metabolism through the lipoxygenase pathway. Here we have identified the eicosanoids that mediate the hydrogen peroxide-induced growth-related events in these cells. Hydrogen peroxide stimulated the production of 12- and 15-hydroperoxyeicosatetraenoic acids in vascular smooth muscle cells. Both 12- and 15-hydroperoxyeicosatetraenoic acids induced the expression of c-Fos and c-Jun protein and increased activating protein 1 (AP-1) activity, as measured by AP-1-DNA binding and AP-1-dependent human collagenase promoter-driven chloramphenicol acetyltransferase reporter gene transcription. Hydrogen peroxide and arachidonic acid also induced the expression of c-Fos and c-Jun protein and AP-1 activity. Nordihydroguaiaretic acid, an inhibitor of the lipoxygenase pathway, significantly inhibited both hydrogen peroxide and arachidonic acid-stimulated c-Fos and c-Jun protein expression and AP-1 activity. Together, these findings suggest that hydrogen peroxide induces the production of eicosanoids and that the eicosanoids are potential mediators of the oxidative stress-stimulated growth-related events in vascular smooth muscle cells.
我们之前报道过，过氧化氢作为一种活性氧和细胞氧化剂，可诱导血管平滑肌细胞中c-Fos和c-Jun mRNA表达以及DNA合成，并且这些过程需要花生四烯酸通过脂氧合酶途径释放和代谢。在此，我们确定了介导过氧化氢诱导这些细胞中生长相关事件的类二十烷酸。过氧化氢刺激血管平滑肌细胞中12-和15-氢过氧二十碳四烯酸的产生。12-和15-氢过氧二十碳四烯酸均诱导c-Fos和c-Jun蛋白的表达，并增加激活蛋白1（AP-1）活性，这通过AP-1-DNA结合以及AP-1依赖的人胶原酶启动子驱动的氯霉素乙酰转移酶报告基因转录来测定。过氧化氢和花生四烯酸也诱导c-Fos和c-Jun蛋白的表达以及AP-1活性。去甲二氢愈创木酸，一种脂氧合酶途径抑制剂，显著抑制过氧化氢和花生四烯酸刺激的c-Fos和c-Jun蛋白表达以及AP-1活性。总之，这些发现表明过氧化氢诱导类二十烷酸的产生，并且类二十烷酸是血管平滑肌细胞中氧化应激刺激的生长相关事件的潜在介质。
