Knockout of cellular glutathione peroxidase gene renders mice susceptible to diquat-induced oxidative stress
Knockout of cellular glutathione peroxidase gene renders mice susceptible to diquat-induced oxidative stress
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DOI：
10.1016/s0891-5849(99)00104-5
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发表时间：
1999-09-01
影响因子：
7.4
通讯作者：
Lei, XG
中科院分区：
文献类型：
--
作者：
Fu, YX;Cheng, WH;Lei, XG
进行了两个实验，以确定细胞谷胱甘肽过氧化物酶（GPX 1）对致死，急性氧化应激诱导的24毫克敌草快/公斤体重腹腔注射的保护和潜在的机制。在实验1中，在硒（Se）充足或缺乏GPX 1敲除小鼠[GPX 1（-/-）]和野生型小鼠（WT）之间比较死亡率和存活时间。在实验2中，来自这四个组的小鼠在注射敌草快后0、1、2和3 h被安乐死，以阐明氧化事件的时程。除Se充足WT外，所有组的应激均产生100%死亡率，在第7天将其安乐死以进行分析。Se缺乏WT和Se充足GPX 1（-/-）具有相似的存活时间（4.1和3.9小时），其比Se缺乏GPX 1（-/-）（2.4小时）长（p <0.05）。然而，这三个GPX 1缺乏组的肝脏F-2-异前列烷和羰基含量和/或血浆丙氨酸氨基转移酶活性水平高于Se充足WT组（p <0.05）。在这些动物中，敌草胺诱导的肝脏F-2-异前列烷形成在1小时达到峰值，并且在硒充足的GPX 1（-/-）中，血浆丙氨酸氨基转移酶升高之前。GPX 1水平影响肝脏超氧化物歧化酶活性对敌草快处理的反应。GPX 1是抗敌草快致死性氧化应激的主要硒蛋白。(C)1999 Elsevier Science Inc.
Two experiments were conducted to determine the protection and the underlying mechanisms of cellular glutathione peroxidase (GPX1) against lethal, acute oxidative stress induced by an intraperitoneal injection of 24 mg diquat/kg body weight. In experiment 1, mortality and survival times were compared among selenium (Se)-adequate or deficient GPX1 knockout mice [GPX1(-/-)] and wild-type mice (WT). In experiment 2, mice from these four groups were euthanized at 0, 1, 2, and 3 h after the injection of diquat to elucidate the time course of oxidative events. The stress produced 100% mortality in all of the groups except for the Se-adequate WT, which were euthanized on day 7 for analysis. The Se-deficient WT and the Se-adequate GPX1(-/-) had similar survival times (4.1 and 3.9 h), which were longer (p < .05) than that of the Se-deficient GPX1(-/-) (2.4 h). However, these three GPX1-deficient groups had higher levels (p < .05) of hepatic F-2-isoprostanes and carbonyl contents and/or plasma alanine aminotransferase activities than those of the Se-adequate WT. The diquat-induced formations of hepatic F-2-isoprostanes in these animals peaked at 1 h and preceded the rise of plasma alanine aminotransferase in the Se-adequate GPX1(-/-). Responses of hepatic superoxide dismutase activities to the diquat treatment were affected by the GPX1 level. In conclusion, GPX1 is the major selenoprotein to protect mice against the lethal oxidative stress induced by diquat. (C) 1999 Elsevier Science Inc.