A redox-sensitive peroxiredoxin that is important for longevity has tissue- and stress-specific roles in stress resistance
A redox-sensitive peroxiredoxin that is important for longevity has tissue- and stress-specific roles in stress resistance
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DOI：
10.1073/pnas.0805507105
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发表时间：
2008-12-16
影响因子：
11.1
通讯作者：
Veal, Elizabeth A.
中科院分区：
文献类型：
--
作者：
Olahova, Monika;Taylor, Sarah R.;Veal, Elizabeth A.
活性氧物质（ROS）引起的氧化损伤与许多疾病以及衰老有关。抗氧化酶对ROS的清除在限制这种损伤方面起着重要作用。例如，过氧化物氧还蛋白（Prx）是一种保守的、含量丰富的硫氧还蛋白过氧化物酶，具有肿瘤抑制功能。除了解毒过氧化物外，在单细胞系统中的研究表明，Prx还可作为分子伴侣和氧化还原传感器。然而，在整个动物体的背景下，Prx的不同活性以何种方式影响抗逆性或寿命尚不清楚。在此，我们揭示了2 - 半胱氨酸过氧化物氧还蛋白PRDX - 2在线虫秀丽隐杆线虫抗逆性中的三种不同作用。（i）PRDX - 2的硫氧还蛋白过氧化物酶活性可抵御过氧化氢。（ii）与过度氧化的PRDX - 2的分子伴侣活性一致，过氧化氢诱导的PRDX - 2氧化增加了对热应激的抗性。（iii）出乎意料的是，PRDX - 2的缺失增加了秀丽隐杆线虫对一些引起氧化应激的物质（如亚砷酸盐）的抗性，这显然是通过一种增加其他抗氧化剂和II相解毒酶水平的信号传导机制实现的。尽管prdx - 2突变体对某些形式的氧化应激的抗性增加，但它们寿命较短。此外，PRDX - 2在肠道中的表达解释了其在外源性过氧化氢解毒中的作用，但不能解释其对亚砷酸盐抗性或寿命的影响，这表明PRDX - 2可能通过不同机制促进寿命并抵御环境应激。这些数据共同表明，在后生动物中，Prx通过多种生化活性发挥作用，并且在抗逆性和寿命方面具有组织特异性功能。
Oxidative damage caused by reactive oxygen species (ROS) is implicated in many diseases and in aging. Removal of ROS by antioxidant enzymes plays an important part in limiting this damage. For instance, peroxiredoxins (Prx) are conserved, abundant, thioredoxin peroxidase enzymes that function as tumor suppressors. In addition to detoxifying peroxides, studies in single-cell systems have revealed that Prx act as chaperones and redox sensors. However, it is unknown in what manner the different activities of Prx influence stress resistance or longevity in the context of whole animals. Here, we reveal three distinct roles for the 2-Cys Prx, PRDX-2, in the stress resistance of the nematode worm Caenorhabditis elegans. (i) The thioredoxin peroxidase activity of PRDX-2 protects against hydrogen peroxide. (ii) Consistent with a chaperone activity for hyperoxidized PRDX-2, peroxide-induced oxidation of PRDX-2 increases resistance to heat stress. (iii) Unexpectedly, loss of PRDX-2 increases the resistance of C. elegans to some oxidative stress-causing agents, such as arsenite, apparently through a signaling mechanism that increases the levels of other antioxidants and phase II detoxification enzymes. Despite their increased resistance to some forms of oxidative stress, prdx-2 mutants are short-lived. Moreover, intestinal expression of PRDX-2 accounts for its role in detoxification of exogenous peroxide, but not its influence on either arsenite resistance or longevity, suggesting that PRDX-2 may promote longevity and protect against environmental stress through different mechanisms. Together the data reveal that in metazoans Prx act through multiple biochemical activities, and have tissue-specific functions in stress resistance and longevity.