NADPH oxidase-dependent signaling in endothelial cells: role in physiology and pathophysiology.
NADPH oxidase-dependent signaling in endothelial cells: role in physiology and pathophysiology.
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DOI：
10.1089/ars.2008.2220
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发表时间：
2009-04
影响因子：
6.6
通讯作者：
Malik AB
中科院分区：
文献类型：
--
作者：
Frey RS;Ushio-Fukai M;Malik AB
包括超氧化物（O2. -）和过氧化氢（H2 O2）的活性氧物质（ROS）是响应于细胞因子、生长因子、G蛋白偶联受体和内皮细胞（EC）中的剪切应力而内源性产生的。活性氧作为信号分子介导内皮细胞的基因表达、细胞增殖、迁移、血管生成、凋亡和衰老等多种生物学反应。活性氧激活的信号转导，即“氧化剂信号传导”，受到了广泛的研究。过量的ROS导致多种病理生理学，包括内皮功能障碍、动脉粥样硬化、高血压、糖尿病和急性呼吸窘迫综合征（ARDS）。EC中ROS的主要来源是NADPH氧化酶。原型吞噬细胞NADPH氧化酶由膜结合的gp 91 phox和p22 hox以及胞质亚基如p47 phox、p67 phox和小GT3 Rac组成。在EC中，除了吞噬NADPH氧化酶的所有组分之外，还表达gp 91 phox（Nox 2）的同系物，包括Nox 1、Nox 4和Nox 5。这篇综述的目的是提供一个概述的新兴领域的活性氧来源于NADPH氧化酶和氧化剂信号在内皮细胞连接到生理和病理生理功能。了解这些机制可能会提供深入了解NADPH氧化酶和氧化剂信号成分作为潜在的治疗靶点。
Reactive oxygen species (ROS) including superoxide (O2.−) and hydrogen peroxide (H2O2) are produced endogenously in response to cytokines, growth factors; G-protein coupled receptors and shear stress in endothelial cells (ECs). ROS function as signaling molecules to mediate various biological responses such as gene expression, cell proliferation, migration, angiogenesis, apoptosis and senescence in ECs. Signal transduction activated by ROS, “oxidant signaling,” has received intense investigation. Excess amount of ROS contribute to various pathophysiologies including endothelial dysfunction, atherosclerosis, hypertension, diabetes and acute respiratory distress syndrome (ARDS). The major source of ROS in EC is a NADPH oxidase. The prototype phagaocytic NADPH oxidase composed of membrane-bound gp91phox and p22hox as well as cytosolic subunits such as p47phox, p67phox and small GTPase Rac. In ECs in addition to all the components of phagocytic NADPH oxidases, homologues of gp91phox (Nox2) including Nox1, Nox4, and Nox5 are expressed. The aim of this review is to provide an overview of the emerging area of ROS derived from NADPH oxidase and oxidant signaling in ECs linked to physiological and pathophysiological functions. Understanding these mechanisms may provide insight into the NADPH oxidase and oxidant signaling components as potential therapeutic targets.
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