文章：

氮氧化物氧化酶在细胞转化中的辅助和辅助作用

Aiding and abetting roles of NOX oxidases in cellular transformation

原文发布日期：2012-08-24

DOI: 10.1038/nrc3339

类型: Review Article

开放获取: 否

要点：

1. As early as 1981, it was suggested that enzymes biochemically similar to the NADPH oxidase (NOX) NOX2 were present in all cell types, not just in neutrophils. A decade later, high levels of superoxide and hydrogen peroxide were found in various cancer cells, and these levels could be reduced by diphenyleneiodonium (DPI), a chemical inhibitor of flavoprotein-containing enzymes, such as NOX oxidases.
2. The mitochondrial electron transfer chain and NADPH oxidases of the NOX family are the two major sources of reactive oxygen species (ROS) that are implicated in cancer.
3. Seven membrane-bound NOX catalytic isoforms (NOX1–5) and dual oxidase 1 (DUOX1) and DUOX2 have been identified, each of which displays similar but distinct structural, biochemical and subcellular localization characteristics.
4. NOX-dependent redox signalling occurs at cellular membranes and intracellular structures where the NOX catalytic and regulatory subunits are localized. The NOX catalytic subunits NOX2, NOX1, NOX4 and NOX5 have been detected in the plasma membrane. NOX4 has additionally been detected in the endoplasmic reticulum, mitochondrial and nuclear membranes. NOX subunits also reside at specific subcellular microdomains, such as NOX4 at focal adhesions, NOX1 at caveoli and lipid rafts, and NOX1 and NOX4 at invadopodia.
5. NOX catalytic and regulatory subunits have been implicated in one or more of the most common cancer types. Increased mRNA and/or protein expression of NOX1, NOX2, NOX4 and NOX5 or their regulatory components have been detected at higher levels in various cultured cancer cell lines or human tumours compared with normal controls at early and late stages of tumorigenesis, suggesting that ROS derived from NADPH oxidases may be important in both the initiation and the maintenance phases of tumour development.
6. Initial studies indicate that NOX oxidases can effect several of the hallmarks of cancer, including genomic instability, autonomous growth and survival, angiogenesis, invasion and metastasis.

要点翻译：

1. 早在一九八一年，就有研究指出与NADPH氧化酶（NOX）NOX2生化特性相似的酶存在于所有细胞类型中，而不仅限于中性粒细胞。十年后，研究人员在多种癌细胞中发现高水平的超氧化物和过氧化氢，且这些活性氧水平可被含黄素蛋白酶（如NOX氧化酶）的化学抑制剂二亚苯基碘鎓（DPI）降低。
2. 线粒体电子传递链和NOX家族的NADPH氧化酶是活性氧（ROS）的两大主要来源，这些活性氧与癌症的发生发展密切相关。
3. 目前已知的NOX催化亚型包括七种膜结合型（NOX1-5）及两种双重氧化酶（DUOX1和DUOX2），它们具有相似但各自独特的结构、生化特性和亚细胞定位特征。
4. NOX依赖的氧化还原信号传导发生在细胞膜和细胞内结构上，这些位置正是NOX催化亚基和调节亚基的定位所在。NOX2、NOX1、NOX4和NOX5催化亚基已在质膜中被检测到，其中NOX4还存在于内质网、线粒体膜和核膜。NOX亚基还定位于特定亚细胞微域：如NOX4位于黏着斑，NOX1位于小窝和脂筏，而NOX1与NOX4均存在于侵袭伪足。
5. NOX催化亚基和调节亚基与一种或多种常见癌症类型相关。在肿瘤发生早期和晚期阶段，与正常对照组相比，多种培养癌细胞系或人类肿瘤组织中NOX1、NOX2、NOX4、NOX5及其调控元件的mRNA和/或蛋白表达均显著上调，这表明NADPH氧化酶衍生的活性氧可能在肿瘤发生的起始阶段和维持阶段均发挥重要作用。
6. 初步研究表明，NOX氧化酶可影响癌症的多个特征性表现，包括基因组不稳定性、自主生长与存活、血管生成、侵袭和转移能力。

英文摘要：

NADPH oxidases of the NADPH oxidase (NOX) family are dedicated reactive oxygen species-generating enzymes that broadly and specifically regulate redox-sensitive signalling pathways that are involved in cancer development and progression. They act at specific cellular membranes and microdomains through the activation of oncogenes and the inactivation of tumour suppressor proteins. In this Review, we discuss primary targets and redox-linked signalling systems that are influenced by NOX-derived ROS, and the biological role of NOX oxidases in the aetiology of cancer.

摘要翻译： 

NADPH氧化酶（NOX）家族是专门的活性氧（ROS）生成酶，能够广泛且特异性地调控与癌症发生和进展相关的氧化还原敏感信号通路。它们通过激活癌基因和失活肿瘤抑制蛋白，作用于特定的细胞膜和微区。在本综述中，我们讨论了NOX来源的ROS影响的主要靶点和氧化还原相关信号系统，以及NOX氧化酶在癌症病因学中的生物学作用。

原文链接：

Aiding and abetting roles of NOX oxidases in cellular transformation