Section of Molecular Medicine, Department of Medicine, and Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Free Radic Biol Med. 2012 May 1;52(9):1607-19. doi: 10.1016/j.freeradbiomed.2012.01.025. Epub 2012 Feb 4.
Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are ubiquitously produced in cardiovascular systems. Under physiological conditions, ROS/RNS function as signaling molecules that are essential in maintaining cardiovascular function. Aberrant concentrations of ROS/RNS have been demonstrated in cardiovascular diseases owing to increased production or decreased scavenging, which have been considered common pathways for the initiation and progression of cardiovascular diseases such as atherosclerosis, hypertension, (re)stenosis, and congestive heart failure. NAD(P)H oxidases are primary sources of ROS and can be induced or activated by all known cardiovascular risk factors. Stresses, hormones, vasoactive agents, and cytokines via different signaling cascades control the expression and activity of these enzymes and of their regulatory subunits. But the molecular mechanisms by which NAD(P)H oxidase is regulated in cardiovascular systems remain poorly characterized. Investigations by us and others suggest that adenosine monophosphate-activated protein kinase (AMPK), as an energy sensor and modulator, is highly sensitive to ROS/RNS. We have also obtained convincing evidence that AMPK is a physiological suppressor of NAD(P)H oxidase in multiple cardiovascular cell systems. In this review, we summarize our current understanding of how AMPK functions as a physiological repressor of NAD(P)H oxidase.
活性氧（ROS）和活性氮（RNS）在心血管系统中广泛产生。在生理条件下，ROS/RNS 作为信号分子发挥作用，对于维持心血管功能至关重要。由于产生增加或清除减少，心血管疾病中 ROS/RNS 的浓度异常，这被认为是动脉粥样硬化、高血压、（再）狭窄和充血性心力衰竭等心血管疾病发生和发展的共同途径。NAD(P)H 氧化酶是 ROS 的主要来源，可被所有已知的心血管危险因素诱导或激活。通过不同的信号级联，应激、激素、血管活性物质和细胞因子控制这些酶及其调节亚基的表达和活性。但是，NAD(P)H 氧化酶在心血管系统中如何被调节的分子机制仍知之甚少。我们和其他人的研究表明，一磷酸腺苷激活蛋白激酶（AMPK）作为能量传感器和调节剂，对 ROS/RNS 高度敏感。我们还获得了令人信服的证据表明，AMPK 是多种心血管细胞系统中 NAD(P)H 氧化酶的生理性抑制剂。在这篇综述中，我们总结了我们目前对 AMPK 如何作为 NAD(P)H 氧化酶的生理性抑制剂发挥作用的理解。
