Increased susceptibility of MER5 (peroxiredoxin III) knockout mice to LPS-induced oxidative stress
Increased susceptibility of MER5 (peroxiredoxin III) knockout mice to LPS-induced oxidative stress
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DOI：
10.1016/j.bbrc.2007.02.022
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发表时间：
2007-04-13
影响因子：
3.1
通讯作者：
Obinata, Masuo
中科院分区：
文献类型：
--
作者：
Li, Lianqin;Shoji, Wataru;Obinata, Masuo
MER 5（peroxiredoxin III，PrxIII）是过氧化物酶家族的一员，具有抗氧化活性。本研究使用MER 5敲除小鼠来研究其体内功能。MER 5基因敲除小鼠出生频率正常，可以生长成熟，但我们发现，在敲除小鼠的巨噬细胞中，细胞内ROS水平显著较高。我们研究了MER 5功能的作用，氧化应激反应的小鼠体内接种脂多糖（LPS）。在基因敲除小鼠中检测到更严重的肺部炎症，如炎性细胞浸润和气道壁增厚。同时，在基因敲除小鼠的肺组织中检测到更强烈的DNA和蛋白质氧化损伤，包括8-羟基-2 '-脱氧鸟苷（8-OHdG）形成和蛋白质羰基化。肺组织炎症和氧化损伤程度与LPS剂量呈正相关。我们的研究结果表明，MER 5基因敲除小鼠细胞内积累的活性氧水平较高，导致I-PS诱导的肺损伤更严重，因此，提示MER 5作为一个重要的清除剂活性氧（ROS）在氧化应激下。(c)2007年爱思唯尔公司All rights reserved.
MER5 (also called peroxiredoxin III, PrxIII) is a member of peroxircdoxin family that has antioxidant activity. The present study was performed to investigate its in vivo function using MER5 knockout mice. MER5 knockout mice were born in normal frequency and could grow to maturity, but we found that intracellular ROS levels are significantly higher in the macrophages of the knockout mice. We examined roles of MER5 function for the oxidative stress responses by intratracheal inoculation of lipopolysaccharide (LPS) to the mice. Lung inflammation such as inflammatory cell infiltration and airway wall thickening was more severely detected in the knockout mice. At the same time, oxidative damage on DNA and proteins was more strongly detected in lung tissues of the knockout mice, including 8-hydroxy-2'-deoxyguanosine (8-OHdG) formation and protein carbonylation. The degrees of lung inflammation and oxidative damage were positively related with LPS doses. Our results indicate that MER5 knockout mice accumulated higher intracellular ROS levels, which cause I-PS-induced lung injury more severely, and thus, Suggested that MER5 acts as an important scavenger of reactive oxygen species (ROS) under oxidative stress. (c) 2007 Elsevier Inc. All rights reserved.