NADPH氧化酶激活机制和病理意义

Mechanisms and pathological significance of activation of NADPH oxidase

活性氧影响许多生理过程,包括宿主防御能力、激素合成和细胞内信号转导等。因活性氧过量而引起的氧化应激涉及高血压、动脉粥样硬化、糖尿病、心肌肥厚、心衰、缺血再灌注损伤、脑卒中和慢性肾病等许多疾病的发生和病理过程。NADPH氧化酶是机体促活性氧生成的主要酶类之一。NADPH氧化酶的激活很复杂,其活性受蛋白激酶、磷脂酶、肌动蛋白、皮质肌动蛋白(皮动蛋白)、冠蛋白和脂质筏等的调节。NADPH氧化酶活性的增高还涉及基因表达水平的上调。因此,阐明NADPH氧化酶活性调节机制将为心血管等疾病的药物防治提供新思路。

Reactive oxygen species（ ROS） affect many physiological processes including host defense,hormone biosynthesis and cellular signaling. Over-production of ROS（ referring to oxidative stress） is involved in various pathological processes including multiple diseases,such as atherosclerosis,cardiac hypertrophy,ischemia-reperfusion injury,hypertension,diabetes,stroke and heart failure.NADPH oxidase（ Nox） is one of the major enzymes to promote the generation of ROS. The mechanisms for activation of Nox are very complicated,which are regulated by multiple factors such as protein kinases,phospholipases,actin,cortactin,coronin,and lipid rafts. The increase of gene expression is also involved in Nox activation. Therefore,elucidation of the regulatory mechanisms for Nox activation will provide new insights into the prevention and therapy of cardiovascular diseases.