In vitro and in vivo protection by melatonin against the decline of elongation factor-2 caused by lipid peroxidation: preservation of protein synthesis
In vitro and in vivo protection by melatonin against the decline of elongation factor-2 caused by lipid peroxidation: preservation of protein synthesis
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DOI：
10.1111/j.1600-079x.2011.00961.x
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发表时间：
2012-08-01
影响因子：
10.3
通讯作者：
Ayala, Antonio
中科院分区：
文献类型：
--
作者：
Argueelles, Sandro;Munoz, Mario F.;Ayala, Antonio
随着生物体的衰老，所有组织中的蛋白质合成都大大减少。在老年动物中翻译下降的可能原因之一是延长因子-2（eEF-2）的修饰。eEF-2在蛋白质合成中发挥重要作用，催化核糖体易位反应。eEF-2对增加的氧化应激特别敏感。然而，所有氧化剂都不影响eEF-2，只有增加脂质过氧化的化合物。由于过氧化物是不稳定的化合物，它们分解并产生一系列高活性化合物，包括醛类、丙二醛（MDA）和4-羟基壬烯醛（HNE）。我们以前曾报道，肝eEF-2形成加合物与低分子量醛，MDA和HNE。因此，eEF-2的保护必须通过具有脂过氧自由基清除功能的化合物（如褪黑激素）进行。在这篇文章中，我们显示了褪黑激素的能力，以防止发生的变化，在eEF-2的条件下的脂质过氧化氢枯烯（CH），实验中使用的化合物诱导脂质分解引起的脂质过氧化反应。作为实验模型，我们使用了培养的细胞和用这种氧化剂化合物处理的大鼠。测定eEF-2水平、该蛋白与MDA和HNE的加合物形成以及脂质过氧化物。在培养的细胞中，还测量了蛋白质合成速率。我们的研究结果表明，褪黑激素防止了eEF-2的分子变化和继发于脂质过氧化的蛋白质合成速率下降。结果还表明，血清中的几种激素水平的影响CH诱导的氧化应激，这是部分或全部由褪黑激素。
As organisms age, a considerable decrease in protein synthesis takes place in all tissues. Among the possible causes of the decline of translation in old animals are the modifications of elongation factor-2 (eEF-2). eEF-2 occupies an essential role in protein synthesis where it catalyzes the ribosomal translocation reaction. eEF-2 is particularly sensitive to increased oxidative stress. However, all oxidants do not affect eEF-2, only compounds that increase lipid peroxidation. As peroxides are unstable compounds, they decompose and generate a series of highly reactive compounds, including aldehydes malondialdehyde (MDA) and 4-hydroxynoenal (HNE). We have previously reported that hepatic eEF-2 forms adducts with low-molecular weight aldehydes, MDA and HNE. Therefore, the protection of eEF-2 must be specifically carried out by a compound with lipoperoxyl radical-scavenging features such as melatonin. In this article, we show the ability of melatonin to protect against the changes that occur in the eEF-2 under conditions of lipid peroxidation induced by cumene hydroperoxide (CH), a compound used experimentally to induce lipid breakdown. As experimental models, we used cultured cells and rats treated with this oxidant compound. eEF-2 levels, adduct formation of this protein with MDA and HNE, and lipid peroxides were determined. In the cultured cells, protein synthesis rate was also measured. Our results show that melatonin prevented the molecular changes in eEF-2 and the decline in protein synthesis rate secondary to lipid peroxidation. The results also show that serum levels of several hormones were affected by CH-induced oxidative stress, which was partially or totally prevented by melatonin.