Methionine sulfoxide reductase A protects neuronal cells against brief hypoxia/reoxygenation
Methionine sulfoxide reductase A protects neuronal cells against brief hypoxia/reoxygenation
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DOI：
10.1073/pnas.0308215100
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发表时间：
2004-02-03
影响因子：
11.1
通讯作者：
Hoshi, T
中科院分区：
文献类型：
--
作者：
Yermolaieva, O;Xu, R;Hoshi, T
缺氧/复氧通过促进氧化应激诱导细胞损伤。蛋氨酸在含有A型蛋氨酸亚砜还原酶(MSRA)的蛋白质中的可逆氧化被认为具有一般的抗氧化作用。因此，我们检测了MSRA的过表达是否能保护细胞免受缺氧/复氧损伤。短暂低氧使PC12细胞内ROS水平升高，促进细胞死亡。腺病毒介导的MSRA过表达显著降低了缺氧诱导的ROS增加，促进了细胞的存活。对PC12细胞完整线粒体膜电位和分离的大鼠肝线粒体膜电位的测定表明，低氧可引起线粒体膜去极化。结果表明，MSRA对缺氧/复氧诱导的细胞损伤具有保护作用，提示了MSRA在缺血性心脑血管疾病中的治疗潜力。
Hypoxia/reoxygenation induces cellular injury by promoting oxidative stress. Reversible oxidation of methionine in proteins involving the enzyme peptide methionine sulfoxide reductase type A (MSRA) is postulated to serve a general antioxidant role. Therefore, we examined whether overexpression of MSRA protected cells from hypoxia/reoxygenation injury. Brief hypoxia increased the intracellular reactive oxygen species (ROS) level in PC12 cells and promoted apoptotic cell death. Adenovirus-mediated overexpression of MSRA significantly diminished the hypoxia-induced increase in ROS and facilitated cell survival. Measurements of the membrane potentials of intact mitochondria in PC12 cells and of isolated rat liver mitochondria showed that hypoxia induced depolarization of the mitochondrial membrane. The results demonstrate that MSRA plays a protective role against hypoxia/reoxygenation-induced cell injury and suggest the therapeutic potential of MSRA in ischemic heart and brain disease.