ROS generation by nonphagocytic NADPH oxidase: Potential relevance in diabetic nephropathy
ROS generation by nonphagocytic NADPH oxidase: Potential relevance in diabetic nephropathy
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DOI：
10.1097/01.asn.0000077406.67663.e7
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发表时间：
2003-08-01
影响因子：
13.6
通讯作者：
Shah, AM
中科院分区：
文献类型：
--
作者：
Li, JM;Shah, AM
氧化应激已成为糖尿病患者发生动脉粥样硬化和肾病等长期并发症的重要致病因素。虽然多种酶和过程可以促进氧化应激，但最近的研究表明，多组分吞噬细胞型NADPH氧化酶是许多非吞噬细胞（包括成纤维细胞、血管平滑肌细胞、内皮细胞、肾系膜细胞和肾小管细胞）中活性氧（ROS）产生的主要来源。在生理条件下，非吞噬细胞NADPH氧化酶具有非常低水平的组成活性。然而，酶活性可响应于诸如生长因子、细胞因子、高葡萄糖和高脂血症的刺激而急性和慢性上调。由氧化酶产生的ROS可能起信号传导作用或可能导致氧化损伤。本文综述了目前的知识，非吞噬细胞NADPH氧化酶在结构和生化水平，并讨论了这些酶在糖尿病肾病的病理生理可能发挥的作用。
Oxidative stress has emerged as an important pathogenic factor in the development of long-term complications, such as atherosclerosis and nephropathy, in patients with diabetes. Whereas multiple enzymes and processes can contribute to oxidative stress, recent studies indicate that a multicomponent phagocyte-type NADPH oxidase is a major source of reactive oxygen species (ROS) production in many nonphagocytic cells, including fibroblasts, vascular smooth muscle cells, endothelial cells, renal mesangial cells, and tubular cells. Under physiologic conditions, nonphagocytic NADPH oxidases have very low-level constitutive activity. However, enzyme activity can be upregulated both acutely and chronically in response to stimuli such as growth factors, cytokines, high glucose, and hyperlipidemia. ROS production by the oxidase may serve a signaling role or may lead to oxidative damage. This article reviews current knowledge of the nonphagocyte-NADPH oxidases at both structural and biochemical levels and discusses the possible role of these enzymes in the pathophysiology of diabetic nephropathy.