The NOX toolbox: validating the role of NADPH oxidases in physiology and disease.
The NOX toolbox: validating the role of NADPH oxidases in physiology and disease.
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DOI：
10.1007/s00018-012-1010-9
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发表时间：
2012-07
影响因子：
8
通讯作者：
Schmidt, Harald H. H. W.
中科院分区：
文献类型：
--
作者：
Altenhofer, Sebastian;Kleikers, Pamela W. M.;Radermacher, Kim A.;Scheurer, Peter;Hermans, J. J. Rob;Schiffers, Paul;Ho, Heidi;Wingler, Kirstin;Schmidt, Harald H. H. W.
活性氧（ROS）是细胞信号，但也是疾病的触发因素;与还原当量相比，它们的相对过量（氧化应激）或短缺（还原应激）可能是有害的。这可以解释为什么抗氧化剂不能对抗与氧化应激相关的疾病。相反，靶向疾病相关的酶活性氧来源，使生理活性氧信号不受影响，可能是更有益的。NADPH氧化酶是唯一已知的具有产生ROS的唯一功能的酶家族。在催化NADPH氧化酶亚基（NOX）中，NOX 4是分布最广的同种型。我们在这里提供了一个关键的审查，目前可用的实验工具，以评估的作用，NOX，特别是NOX 4，即敲除小鼠，siRNA，抗体和药理学抑制剂。然后，我们专注于表征的小分子NADPH氧化酶抑制剂，VAS 2870，在体外和体内，其特异性，选择性，和可能的作用机制。最后，我们讨论了NOX 4作为中风、心力衰竭和纤维化等适应症的潜在治疗靶点的验证。
Reactive oxygen species (ROS) are cellular signals but also disease triggers; their relative excess (oxidative stress) or shortage (reductive stress) compared to reducing equivalents are potentially deleterious. This may explain why antioxidants fail to combat diseases that correlate with oxidative stress. Instead, targeting of disease-relevant enzymatic ROS sources that leaves physiological ROS signaling unaffected may be more beneficial. NADPH oxidases are the only known enzyme family with the sole function to produce ROS. Of the catalytic NADPH oxidase subunits (NOX), NOX4 is the most widely distributed isoform. We provide here a critical review of the currently available experimental tools to assess the role of NOX and especially NOX4, i.e. knock-out mice, siRNAs, antibodies, and pharmacological inhibitors. We then focus on the characterization of the small molecule NADPH oxidase inhibitor, VAS2870, in vitro and in vivo, its specificity, selectivity, and possible mechanism of action. Finally, we discuss the validation of NOX4 as a potential therapeutic target for indications including stroke, heart failure, and fibrosis.
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