Glutathione is essential to preserve nuclear function and cell survival under oxidative stress
Glutathione is essential to preserve nuclear function and cell survival under oxidative stress
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DOI：
10.1016/j.freeradbiomed.2013.10.807
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发表时间：
2014-02-01
影响因子：
7.4
通讯作者：
Chedin, Stephane
中科院分区：
文献类型：
--
作者：
Hatem, Elie;Berthonaud, Veronique;Chedin, Stephane
谷胱甘肽（GSH）被认为是细胞最重要的氧化还原缓冲剂。为了更好地表征其在氧化应激条件下的基本功能，我们研究了过氧化氢处理的酵母细胞含有不同数量的GSH的生理反应。我们发现，GSH耗竭细胞的转录反应是严重受损，尽管有效的核积累的转录因子Yap1。此外，氧化应激在GSH耗尽的细胞中产生高基因组不稳定性，但不激活检查点激酶Rad53。令人惊讶的是，在H2O2处理下，细胞内GSH的稀缺量足以保持细胞活力。在这些细胞中，氧化应激仍然导致氧化蛋白的积累和翻译活性的失活，但核组分和活性受到保护，免受氧化损伤。我们的结论是，谷胱甘肽的重要作用是保护核功能，使细胞的生存和生长恢复后，氧化应激释放。我们认为，胞浆蛋白是一种保护机制的一部分，它通过清除活性氧来保护细胞核，然后才能穿过核膜。(C)2013 Elsevier Inc. All rights reserved.
Glutathione (GSH) is considered the most important redox buffer of the cell. To better characterize its essential function during oxidative stress conditions, we studied the physiological response of H2O2-treated yeast cells containing various amounts of GSH. We showed that the transcriptional response of GSH-depleted cells is severely impaired, despite an efficient nuclear accumulation of the transcription factor Yap1. Moreover, oxidative stress generates high genome instability in GSH-depleted cells, but does not activate the checkpoint kinase Rad53. Surprisingly, scarce amounts of intracellular GSH are sufficient to preserve cell viability under H2O2 treatment In these cells, oxidative stress still causes the accumulation of oxidized proteins and the inactivation of the translational activity, but nuclear components and activities are protected against oxidative injury. We conclude that the essential role of GSH is to preserve nuclear function, allowing cell survival and growth resumption after oxidative stress release. We propose that cytosolic proteins are part of a protective machinery that shields the nucleus by scavenging reactive oxygen species before they can cross the nuclear membrane. (C) 2013 Elsevier Inc. All rights reserved.