Vascular function of the Cytochrome P450 reductase (POR)

活性氧（ROS）失衡引起的氧化应激被认为是心血管疾病（CVD）的重要诱因。NADPH氧化酶（Nox）是ROS的来源。它们在CVD中的作用来自转基因动物的研究，非特异性抑制剂，但主要来自nadph刺激试验。在这些实验中，从细胞或组织分离的膜中补充NADPH以重现体外Nox活性。然而，这样的分析表明，申请人不测量氮氧化物，但细胞色素P450还原酶（POR）活性。该酶与Nox酶具有结构上的相似性，而由Nox酶引起的血管效应可能是由POR介导的。因此，由于POR和Noxes的巧合，后者成为CVD中氧化应激的重要来源，从而成为药理学靶点，而另一种酶在很大程度上被忽视了。在目前的应用中，POR的血管功能及其对检测信号的贡献将通过转基因动物、细胞培养研究和生化分析来确定。

Oxidative stress caused by imbalanced reactive oxygen species (ROS) is being seen as a strong contributor to cardiovascular diseases (CVD). NADPH oxidase enzymes (Nox) are sources of ROS. Their role in CVD emerged from studies using transgenic animals, unspecific inhibitors but largely from NADPH-stimulated assays. In these assays, membranes isolated from cell or tissue were supplemented with NADPH to recapitulate Nox activity in vitro. Such assays, however, were shown by the applicant not to measure Nox but cytochrome P450 reductase (POR) activity. This enzyme shares structural similarities with Nox enzymes and the vascular effects, which were attributed to Nox enzymes, are potentially mediated by POR. Thus, by an (un)lucky coincidence between POR and Noxes, the later emerged as an important source of oxidative stress in CVD and thus became a pharmacological target, whereas the other enzyme was largely neglected. In the current application, the vascular function of POR and its contribution to assay signal will be identified using transgenic animals, cell culture studies and biochemical assays.