Overexpression of Methionine Sulfoxide Reductases A and B2 Protects MOLT-4 Cells Against Zinc-Induced Oxidative Stress
Overexpression of Methionine Sulfoxide Reductases A and B2 Protects MOLT-4 Cells Against Zinc-Induced Oxidative Stress
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DOI：
10.1089/ars.2008.2102
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发表时间：
2009-02-01
影响因子：
6.6
通讯作者：
Petropoulos, Isabelle
中科院分区：
文献类型：
--
作者：
Cabreiro, Filipe;Picot, Cedric R.;Petropoulos, Isabelle
在氨基酸中，蛋氨酸最容易被氧化，蛋氨酸亚砜还原酶A （MsrA）和B （MsrB）可以在蛋白质内部催化还原蛋氨酸亚砜。作为为数不多的氧化蛋白修复系统之一，MsrA和MsrB酶在衰老过程中的蛋白质稳态中发挥重要作用，并通过清除活性氧参与细胞对氧化应激的防御。为了阐明锌在Msr系统中的作用，我们分析了锌处理对控制和稳定过表达MsrA和MsrB2的MOLT-4白血病细胞的影响。在这里，我们发现锌处理通过诱导金属硫蛋白的转录和正向调节Msr酶的活性，在MOLT-4细胞中具有促抗氧化作用。相反，由于其促氧化作用，锌也导致细胞死亡、活性氧产生和蛋白质损伤增加。我们的研究结果表明，由于其抗氧化特性，Msr酶的过度表达抵消了锌处理的促氧化作用，锌处理通过减少活性氧的产生，导致细胞免受蛋白质氧化损伤和细胞死亡。Antioxid。氧化还原信号，11,215-225。
Among the amino acids, methionine is the most susceptible to oxidation, and methionine sulfoxide can be catalytically reduced within proteins by methionine sulfoxide reductase A (MsrA) and B (MsrB). As one of the very few repair systems for oxidized proteins, MsrA and MsrB enzymes play a major role in protein homeostasis during aging and have also been involved in cellular defenses against oxidative stress, by scavenging reactive oxygen species. To elucidate the role of zinc on the Msr system, the effects of zinc treatment on control and stably overexpressing MsrA and MsrB2 MOLT-4 leukemia cells have been analyzed. Here we show that zinc treatment has a pro-antioxidant effect in MOLT-4 cells by inducing the transcription of metallothioneins and positively modulating the activity of the Msr enzymes. In contrast, due to its pro-oxidant effect, zinc also led to increased cell death, reactive oxygen species production, and protein damage. Our results indicate that overexpression of the Msr enzymes, due to their antioxidant properties, counteracts the pro-oxidant effects of zinc treatment, which lead to a cellular protection against protein oxidative damage and cell death, by reducing the production of reactive oxygen species. Antioxid. Redox Signal. 11, 215-225.