Department of Medical Chemistry, Semmelweis University, Budapest, Hungary.
Antioxid Redox Signal. 2012 Sep 15;17(6):890-901. doi: 10.1089/ars.2011.4161. Epub 2012 Apr 17.
Increased oxidative stress is associated with various diseases and aging, while adaptation to heat stress is an important determinant of survival and contributes to longevity. However, the impact of oxidative stress on heat resistance remains largely unclear.
In this study we investigated how oxidative stress impinges on heat stress responses.
We report that hydrogen-peroxide (H(2)O(2)) pretreatment inhibits both acquired thermotolerance and heat-induced Hsp70 expression in mammalian cells, as well as acquired thermotolerance in the nematode Caenorhabditis elegans, via RNA interference. Moreover, we demonstrate that elimination of RNA interference by silencing key enzymes in microRNA biogenesis, dcr-1 or pash-1, restores the diminished intrinsic thermotolerance of aged and H(2)O(2)-elimination compromised (catalase-2 and peroxiredoxin-2 deficient) worms.
These results uncover a novel post-transcriptional element in the regulation of heat stress adaptation under oxidative conditions that may have implications in disease susceptibility and aging.
氧化应激与各种疾病和衰老有关,而适应热应激是生存的重要决定因素,并有助于长寿。然而,氧化应激对耐热性的影响在很大程度上仍不清楚。
在这项研究中,我们研究了氧化应激如何影响热应激反应。
我们报告说,过氧化氢(H2O2)预处理通过 RNA 干扰抑制哺乳动物细胞中的获得性耐热性和热诱导的 Hsp70 表达,以及线虫秀丽隐杆线虫中的获得性耐热性。此外,我们证明通过沉默 microRNA 生物发生中的关键酶 dcr-1 或 pash-1 消除 RNA 干扰,可以恢复因年龄增长和 H2O2 消除(过氧化氢酶-2 和过氧化物酶-2 缺乏)而受损的内在耐热性。
这些结果揭示了在氧化条件下调节热应激适应的一种新的转录后元件,这可能对疾病易感性和衰老有影响。