Cave Alison
Medicines Health and Regulatory Agency, Market Towers, 1 Nine Elms Lane, London SW8 5NQ, United Kingdom.
Curr Opin Pharmacol. 2009 Apr;9(2):208-13. doi: 10.1016/j.coph.2008.10.001. Epub 2008 Nov 14.
The NADPH oxidase is a ubiquitously distributed multisubunit enzyme which generates superoxide from molecular oxygen using NADPH as the electron donor. In cardiovascular cells the main catalytic unit consists of two subunits, p22(phox) and one of five Nox isoforms, of which Nox1, Nox2 and Nox4 are the main isoforms expressed in cardiovascular cells. Nox1 and Nox2 require the association with cytosolic subunits for activity, whereas Nox4 appears to be constitutively active. Not only does the expression profile of these isoforms differ between different cell types, but individual isoforms appear to have distinct and separate locations within the cell. Nox enzymes have been linked to a range of cardiovascular pathologies including cardiac and vascular hypertrophy and fibrosis, atherosclerosis, vascular inflammation and angiogenesis, in addition to cellular proliferation and differentiation. Moreover, it is becoming increasingly clear that the individual Nox isoforms have delineated roles within the cell and are linked with specific downstream effects. This review will highlight some of the most important recent studies and discuss how specifically targeting the subunits of the NADPH oxidase complex may have therapeutic potential.
NADPH氧化酶是一种广泛分布的多亚基酶，它以NADPH作为电子供体，将分子氧转化为超氧化物。在心血管细胞中，主要的催化单元由两个亚基组成，即p22(phox)和五种Nox同工型之一，其中Nox1、Nox2和Nox4是心血管细胞中表达的主要同工型。Nox1和Nox2需要与胞质亚基结合才能发挥活性，而Nox4似乎具有组成性活性。这些同工型的表达谱不仅在不同细胞类型之间存在差异，而且单个同工型在细胞内似乎具有不同且独立的定位。Nox酶与一系列心血管疾病相关，包括心脏和血管肥大及纤维化、动脉粥样硬化、血管炎症和血管生成，此外还与细胞增殖和分化有关。此外，越来越清楚的是，单个Nox同工型在细胞内具有明确的作用，并与特定的下游效应相关。本综述将重点介绍一些最近最重要的研究，并讨论特异性靶向NADPH氧化酶复合物的亚基可能具有的治疗潜力。
