Reactive Oxygen Species Signaling By Endothelial NOS

一氧化氮合酶，负责底物L-精氨酸产生一氧化氮(NO)的酶，也是NADPH氧化酶。在无细胞体系中，其中一些酶已被证明能产生超氧化物等活性氧物种。在本研究中，我们用人内皮型一氧化氮合酶(ENOS)基因转染人单核细胞U937细胞，发现肿瘤坏死因子α的产生增加，但这种作用与一氧化氮的产生无关。进一步的工作发现，eNOS通过产生一种活性氧物种(ROS)上调TNFa(J Biol Chem，2000)。最近的实验表明，eNOS上调肿瘤坏死因子α是通过依赖超氧化物激活p44/42丝裂原活化蛋白激酶来实现的(Am J Physiol Cell Physiol，2001)。未来的工作将集中在调节eNOS产生NO或ROS的转换机制(S)上。一项密切相关的工作将研究eNOS对内皮细胞炎症反应的调控，以及NO和ROS所扮演的相关角色。

Nitric oxide synthases (NOS), the enzymes responsible for nitric oxide (NO) production from the substrate L-arginine, are also NADPH oxidases. In cell-free systems, some of these enzymes have been shown to produce reactive oxygen species such as superoxide. In this investigation, we transfected monoblastoid U937 cells with human endothelial NOS (eNOS) and found that TNFalpha production was increased, but that this effect was not related to NO production. Further work found that eNOS upregulates TNFa by producing a reactive oxygen species (ROS), (J Biol Chem, 2000). Recent experiments have demonstrated that eNOS upregulation of TNFalpha occurs through superoxide-dependent activation of p44/42 mitogen activated protein kinase (Am J Physiol Cell Physiol, 2001). Future work will focus on the switching mechanism(s) that regulate eNOS to produce either NO or ROS. A closely related effort will examine eNOS modulation of inflammatory responses in endothelial cells and the relative roles played by NO and ROS.