Antioxidant 1 in hypertension: more than just a copper chaperone.
Antioxidant 1 in hypertension: more than just a copper chaperone.
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高血压中的抗氧化剂 1：不仅仅是铜伴侣。
DOI：
10.1161/hypertensionaha.112.191304
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Didion,SeanP
中科院分区：
文献类型：
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作者：
Didion,SeanP
氧化应激，定义为活性氧的增加，与许多疾病有关，包括高血压。超氧化物是心血管系统中特别有害的活性氧物质，因为它直接与NO反应，从而限制了通常可用于诸如内皮依赖性舒张的过程的NO的量。超氧化物歧化酶（SOD）是对抗氧化应激的第一线防御酶，通过其代谢（歧化）调节超氧化物的增加。哺乳动物中存在三种不同的SOD亚型，CuZn-SOD（主要位于细胞质空间）、MnSOD（线粒体中的主要亚型）和细胞外SOD（SOD 3），一种仅在细胞外室发现的CuZnSOD（图）。事实上，有3种不同的基因产物催化相同的反应，强调了限制细胞超氧化物的重要性。CuZnSOD和SOD 3都需要铜来实现完全的催化活性;然而，游离铜基本上是不存在的（每个细胞铜有1个铜离子）。2因此，含铜酶依赖于许多蛋白质，包括铜转运蛋白、铜清除剂和铜“伴侣”，以适当地递送铜。3迄今为止，已鉴定出2种哺乳动物铜分子伴侣，CuZnSOD的铜分子伴侣将铜（顾名思义）传递给CuZnSOD，而抗氧化剂1（Atox 1）将铜传递给跨高尔基体网络和SOD 3。4虽然氧化应激反映了超氧化物的产生和代谢，但大多数研究主要集中在产生超氧化物的酶上，最明显的是NADPH氧化酶。相反，以前的研究没有考虑Atox 1和SOD 3表达/活性在高血压中的关系。在本期《高血压》杂志中，Ozumi等5提供了关于Atox-1在限制血管紧张素II（Ang II）引起的高血压和内皮功能障碍中的作用的一些第一批数据。作者发现，急性（7天）血管紧张素II输注与血管SOD 3表达和活性的选择性增加有关。
Oxidative stress, defined as an increase in reactive oxygen species, has been implicated in a number of diseases, including hypertension. Superoxide is a particularly detrimental reactive oxygen species in the cardiovascular system because it reacts directly with NO, thereby limiting the amount of NO normally available for processes such as endothelium-dependent relaxation. Superoxide dismutases (SODs) represent a first-line defense against oxidative stress by tempering increases in superoxide via its metabolism (dismutation).Three distinct mammalian isoforms of SOD exist, CuZn-SOD (localized mainly to the cytoplasmic space), MnSOD (the predominant isoform in mitochondria), and extracellular SOD (SOD3), a CuZnSOD found exclusively in the extracellular compartment (Figure). 1 The fact that there are 3 different gene products that catalyze the same reaction underscores the importance of limiting cellular superoxide. Both CuZnSOD and SOD3 require copper for full catalytic activity; however, free copper is essentially nonexistent (1 copper ion per cell copper). 2 Thus, copper-containing enzymes are dependent on a number of proteins, including copper transporters, copper scavengers, and copper “chaperones” for appropriate delivery of copper. 3 To date, 2 mammalian copper chaperones have been identified, copper chaperone for CuZnSOD delivers copper as its name would imply to CuZnSOD, whereas antioxidant 1 (Atox1) delivers copper to the transgolgi network and SOD3. 4 Although oxidative stress reflects both production and metabolism of superoxide, a majority of studies have focused primarily on those enzymes that produce superoxide, most notably NADPH oxidase. In contrast, no previous studies have considered the relationship between Atox1 and SOD3 expression/activity in hypertension. In this issue of Hypertension, Ozumi et al5 provide some of the first data regarding the role of Atox-1 in limiting hypertension and endothelial dysfunction produced by angiotensin II (Ang II). The authors found that acute (7-day) Ang II infusion was associated with a selective increase in vascular SOD3 expression and activity