Maternally administered lipopolysaccharide (LPS) upregulates the expression of heme oxygenase-1 in fetal liver: The role of reactive oxygen species
Maternally administered lipopolysaccharide (LPS) upregulates the expression of heme oxygenase-1 in fetal liver: The role of reactive oxygen species
复制标题
母体给予脂多糖 (LPS) 上调胎儿肝脏中血红素加氧酶 1 的表达：活性氧的作用
DOI：
10.1016/j.toxlet.2007.10.010
复制
发表时间：
2008-02-15
影响因子：
3.5
通讯作者：
Xu, De-Xiang
中科院分区：
文献类型：
--
作者：
Li, Xiang-Yun;Zhang, Cheng;Xu, De-Xiang
血红素加氧酶-1（HO-1）是一种诱导型酶，催化血红素降解为胆绿素、一氧化碳和铁的限速步骤。以往的研究表明脂多糖（lipopolysaccharide，LPS）可上调成年小鼠肝脏HO-1的表达。本研究旨在探讨母体内毒素暴露对胎肝HO-1表达的影响。孕鼠在妊娠第17天腹腔注射不同剂量的LPS（1、10、75 μ g/kg）。结果表明，HO-1在胎肝中的表达从LPS后2 h开始增加，LPS后24 h达到最高水平，LPS后持续升高至48 It，而HO-2在各观察时间点均无变化。LPS诱导的HO-I上调被α-苯基-N-叔丁基硝酮（PBN），一种自由基自旋捕获剂阻断。相应地，PBN预处理显着减弱LPS诱导的脂质过氧化和谷胱甘肽（GSH）耗竭胎肝。然而，氨基胍（AG），诱导型一氧化氮合酶（iNOS）的选择性抑制剂，和戊茶碱（PTX），肿瘤坏死因子α（TNF-α）合成的抑制剂，LPS诱导的HO-1在胎肝上调没有影响。总之，活性氧（ROS），而不是TNF-α或一氧化氮（NO），参与LPS诱导的HO-1在胎肝中的上调。这些结果提供了新的证据表明，母体LPS暴露导致胎儿的氧化应激，这可能有助于LPS诱导的发育毒性。(c)2008年由Elsevier爱尔兰有限公司出版。
Heme oxygenase-1 (HO-1) is an inducible enzyme that catalyzes the rate-limiting step in the degradation of heme to biliverdin, carbon monoxide and iron. Previous studies have demonstrated that lipopolysaccharide (LPS) upregulates the expression of HO-1 in adult mouse liver. The present study aimed to investigate the effects of maternal LPS exposure on the expression of HO-1 in fetal liver. The pregnant mice were intraperitoneally injected with different doses of LPS (1, 10, 75 mu g/kg) on gestational day 17. Results showed that the expression of HO-1 in fetal liver was increased, beginning 2 h after LPS, being at the highest level 24 h after LPS, and remaining elevated up to 48 It after LPS, whereas HO-2, the constitutive form, did not change at the various time points observed. LPS-induced upregulation of HO-I was blocked by alpha-phenyl-N-t-butylnitrone (PBN), a free radical spin trapping agent. Correspondingly, PBN pretreatment significantly attenuated LPS-induced lipid peroxidation and glutathione (GSH) depletion in fetal liver. However, aminoguanidine (AG), a selective inhibitor of inducible nitric oxide synthase (iNOS), and pentoxifylline (PTX), an inhibitor of tumor necrosis factor alpha (TNF-alpha) synthesis, had no effect on LPS-induced upregulation of HO-1 in fetal liver. In conclusion, reactive oxygen species (ROS), rather than TNF-alpha or nitric oxide (NO), are involved in LPS-induced upregulation of HO-1 in fetal liver. These results provide new evidence that maternal LPS exposure results in oxidative stress in fetuses, which may contribute to LPS-induced developmental toxicity. (c) 2008 Published by Elsevier Ireland Ltd.