Wessels D A, Hempel S L
Department of Veterans Affairs Medical Center, University of Iowa, Iowa City 52242, USA.
Am J Physiol. 1996 Dec;271(6 Pt 1):C1879-86. doi: 10.1152/ajpcell.1996.271.6.C1879.
Human endothelial cells exposed to H2O2 demonstrate decreased prostacyclin (PGI2) synthesis due to decreased prostaglandin H synthase (PGH synthase) activity. We tested the hypothesis that PGH synthase activity could be protected from H2O2 by a reversible nonsteroidal anti-inflammatory drug. Experiments demonstrate that ibuprofen if present during H2O2 exposure, protects endothelial cell PGH synthase against the decrease in prostaglandin formation caused by H2O2. Additional studies demonstrated that decreasing arachidonic acid release from cell phospholipids during H2O2 exposure did not protect PGI2 synthesis following H2O2 exposure. In other experiments, ibuprofen did not chelate Fe2+ in a conformation that inhibited the reactivity of Fe2+. In addition, ibuprofen did not scavenge HO. However, we demonstrate that ibuprofen significantly protects purified PGH synthase cyclooxygenase activity from the effects of H2O2. The results confirm the hypothesis. These findings suggest that ibuprofen displaces oxidant species from the cyclooxygenase site of PGH synthase, thereby preventing oxidation of the functional groups important for PGH synthase activity.
暴露于过氧化氢的人内皮细胞由于前列腺素H合酶（PGH合酶）活性降低，其前列环素（PGI2）合成减少。我们测试了一种假设，即可逆性非甾体抗炎药可保护PGH合酶活性免受过氧化氢的影响。实验表明，在过氧化氢暴露期间存在布洛芬可保护内皮细胞PGH合酶，使其免受过氧化氢引起的前列腺素生成减少的影响。进一步的研究表明，在过氧化氢暴露期间减少细胞磷脂中花生四烯酸的释放，并不能保护过氧化氢暴露后的PGI2合成。在其他实验中，布洛芬不会以抑制Fe2+反应性的构象螯合Fe2+。此外，布洛芬不会清除羟基自由基。然而，我们证明布洛芬可显著保护纯化的PGH合酶环氧化酶活性免受过氧化氢的影响。结果证实了这一假设。这些发现表明，布洛芬可将氧化剂从PGH合酶的环氧化酶位点置换出来，从而防止对PGH合酶活性重要的官能团发生氧化。
