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首页> 外文期刊>Aging cell. >A peroxiredoxin, PRDX-2, is required for insulin secretion and insulin/IIS-dependent regulation of stress resistance and longevity
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A peroxiredoxin, PRDX-2, is required for insulin secretion and insulin/IIS-dependent regulation of stress resistance and longevity

机译：胰岛素分泌和胰岛素/ IIS依赖的应激抗性和寿命调节需要过氧化物酶PRDX-2

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摘要

Peroxiredoxins (Prx) are abundant thiol peroxidases with a conserved anti-ageing role. In contrast to most animals, the nematode worm, Caenorhabditis elegans, encodes a single cytosolic 2-Cys Prx, PRDX-2, rendering it an excellent model for examining how peroxiredoxins affect animal physiology and ageing. Our previous work revealed that, although PRDX-2 protects against the toxicity of peroxides, enigmatically, prdx-2-mutant animals are hyper-resistant to other forms of oxidative stress. Here, we have investigated the basis for this increased resistance. Mammalian FOXO and Nrf2 transcription factors directly promote the expression of a range of detoxification enzymes. We show that the FOXO orthologue, DAF-16, and the Nrf2 orthologue, SKN-1, are required for the increased stress resistance of prdx-2-mutant worms. Our data suggest that PRDX-2 is required for normal levels of insulin secretion and hence the inhibition of DAF-16 and SKN-1 by insulin/IGF-1-like signalling (IIS) under nutrient-rich conditions. Intriguingly, loss of PRDX-2 increases DAF-16 and SKN-1 activities sufficiently to increase arsenite resistance without initiating other IIS-inhibited processes. Together, these data suggest that loss of peroxiredoxin function may increase stress resistance by reducing insulin secretion, but that further changes in insulin signalling are required for the reprogramming of development and fat metabolism. In addition, we reveal that the temperature-dependent prolongevity function of PRDX-2 is required for the extended lifespan associated with several pathways, including further reductions in IIS.
机译：过氧化物酶（Prx）是丰富的硫醇过氧化物酶，具有保守的抗衰老作用。与大多数动物相反，线虫秀丽隐杆线虫编码单个胞质2-Cys Prx PRDX-2，使其成为研究过氧化物酶如何影响动物生理和衰老的极佳模型。我们以前的工作表明，尽管PRDX-2可以防止过氧化物的毒性，但prdx-2-突变动物对其他形式的氧化应激具有超强的抵抗力。在这里，我们研究了这种增加的阻力的基础。哺乳动物的FOXO和Nrf2转录因子直接促进多种排毒酶的表达。我们表明，FOXO直向同源物DAF-16和Nrf2直向同源物SKN-1是增加prdx-2-mutant蠕虫抗逆性所需的。我们的数据表明PRDX-2是正常水平的胰岛素分泌所必需的，因此在营养丰富的条件下，胰岛素/ IGF-1样信号传导（IIS）对DAF-16和SKN-1的抑制作用。有趣的是，PRDX-2的丧失会充分提高DAF-16和SKN-1的活性，从而增加亚砷酸盐的抗性，而无需启动其他受IIS抑制的过程。总之，这些数据表明过氧化物酶的功能丧失可能通过减少胰岛素分泌而增加抗逆性，但是胰岛素信号的进一步改变对于发育和脂肪代谢的重新编程是必需的。此外，我们揭示PRDX-2的温度依赖性延长功能对于延长与几种途径相关的寿命（包括进一步降低IIS）是必需的。

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