Reactive oxygen species and the control of vascular function.
Reactive oxygen species and the control of vascular function.
复制标题
DOI：
10.1152/ajpheart.01167.2008
复制
发表时间：
2009-03
期刊：
影响因子：
--
通讯作者：
M. Wolin
中科院分区：
文献类型：
--
作者：
M. Wolin
本文总结了活性氧（ROS）和氧化还原信号机制如何参与调节血管平滑肌功能的观点，这些观点是我们在过去25年的研究成果，包括氧传感和可溶性鸟苷酸环化酶（sGC）对cGMP产生的调节，这些研究在2008年实验生物学会议上发表在Robert M. Berne杰出讲座上。它考虑了通过生理刺激、血管疾病过程以及与NAD(P)H氧化还原和缺氧相关的代谢机制来控制包括Nox氧化酶和线粒体在内的ROS来源活性的机制。个体ROS（如过氧化氢）与细胞过氧化氢代谢酶的代谢相互作用被视为影响细胞信号系统的一些最敏感的方式。胞质内NADPH氧化还原的控制似乎也是牛冠状动脉缺氧松弛的主要原因，其氧化作用协调细胞内钙的降低，而肺动脉中胞质内NADPH生成的增加似乎维持了Nox氧化酶活性的升高和过氧化氢的松弛，过氧化氢被缺氧减弱。sGC对一氧化氮的敏感性似乎是由细胞质NADPH控制的硫醇和血红素氧化还原系统调节的。血红素的生物合成和代谢也是调节sGC系统的重要因素。控制氧化酶及其与氧化还原调节系统共定位的信号通路能够选择性激活许多调节机制，影响生理过程中的血管功能和衰老相关血管疾病的进展。
This article summarizes perspectives on how reactive oxygen species (ROS) and redox signaling mechanisms participate in regulating vascular smooth muscle function that have resulted from our studies over the past 25 years in areas including oxygen sensing and the regulation of cGMP production by soluble guanylate cyclase (sGC) that were presented in the Robert M. Berne Distinguished Lectureship at the 2008 Experimental Biology Meeting. It considers mechanisms controlling the activity of sources of ROS including Nox oxidases and mitochondria by physiological stimuli, vascular diseases processes, and metabolic mechanisms linked to NAD(P)H redox and hypoxia. Metabolic interactions of individual ROS such as hydrogen peroxide with cellular peroxide metabolizing enzymes are viewed as some of the most sensitive ways of influencing cellular signaling systems. The control of cytosolic NADPH redox also seems to be a major contributor to bovine coronary arterial relaxation to hypoxia, where its oxidation functions to coordinate the lowering of intracellular calcium, whereas increased cytosolic NADPH generation in pulmonary arteries appears to maintain elevated Nox oxidase activity, and relaxation to hydrogen peroxide, which is attenuated by hypoxia. The sensitivity of sGC to nitric oxide seems to be regulated by thiol and heme redox systems controlled by cytosolic NADPH. Heme biosynthesis and metabolism are also important factors regulating the sGC system. The signaling pathways controlling oxidases and their colocalization with redox-regulated systems enables selective activation of numerous regulatory mechanisms influencing vascular function in physiological processes and the progression of aging-associated vascular diseases.