Vascular function of the Cytochrome P450 reductase (POR)

细胞色素 P450 还原酶 (POR) 的血管功能

• 批准号: 434559990
• 负责人: Dr. Flávia Rezende
• 金额: --
• 依托单位: Institut für Kardiovaskuläre Physiologie (Physiologie I)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/434559990?language=en
• 关键词: Vascular; function; Cytochrome; P450; reductase

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.

由不平衡的活性氧(ROS)引起的氧化应激被认为是心血管疾病(CVD)的重要因素。NADPH氧化酶(NOx)是ROS的来源。它们在心血管疾病中的作用来自于使用转基因动物的研究，非特异性抑制剂，但主要来自NADPH刺激的测试。在这些检测中，从细胞或组织分离的膜上添加NADPH来概括体外的NOx活性。然而，申请人证明，这种检测方法不是测量NOx，而是细胞色素P450还原酶(POR)活性。这种酶在结构上与NOx酶有相似之处，并且被归因于NOx酶的血管效应可能由POR介导。因此，由于POR和NOX之间的幸运巧合，后者成为CVD中氧化应激的重要来源，从而成为一个药理靶点，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鉴定。