Lipopolysaccharide (LPS) up-regulates the expression of haem oxygenase-1 in mouse placenta
Lipopolysaccharide (LPS) up-regulates the expression of haem oxygenase-1 in mouse placenta
复制标题
脂多糖（LPS）上调小鼠胎盘中血红素加氧酶-1的表达
DOI：
10.1016/j.placenta.2007.04.003
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发表时间：
2007-08-01
期刊：
影响因子：
3.8
通讯作者：
Xu, D-X
中科院分区：
文献类型：
--
作者：
Zhang, C.;Li, X.-Y.;Xu, D-X
血红素加氧酶-1（HO-1）是一种诱导酶，催化血红素降解为胆绿素、一氧化碳和铁的限速步骤。越来越多的证据表明HO在细胞防御氧化应激和促炎细胞因子的有害作用中起重要作用。本研究观察了脂多糖（LPS）对小鼠胎盘HO-1表达的影响。当单剂量LPS（75 μ g/kg，i. p.）结果显示，LPS处理后12 h，小鼠胎盘HO-1表达明显增加，至48 h时仍保持较高水平。HO-2的表达，组成型，在观察的各个时间点没有变化。用自由基自旋捕捉剂α-苯基-N-叔丁基硝酮（PBN）预处理孕鼠，可阻断LPS诱导的胎盘HO-1表达上调。相应地，PBN预处理显着抑制LPS诱导的脂质过氧化反应和谷胱甘肽（GSH）消耗在小鼠胎盘。此外，戊茶碱（PTX），肿瘤坏死因子α（TNF-α）合成的抑制剂，也显着衰减LPS诱导的胎盘HO-1的上调。然而，氨基胍（AG），诱导型一氧化氮合酶（NOS）的选择性抑制剂，对LPS诱导的小鼠胎盘HO-1的上调几乎没有影响。这些结果表明，LPS上调小鼠胎盘HO-1的表达。LPS诱导的胎盘HO-1上调可能至少部分由活性氧（ROS）和TNF-α介导，而不是一氧化氮。(c)2007年由Elsevier Ltd.出版
Haem oxygenase-1 (HO-1) is an inducible enzyme that catalyses the rate-limiting step in the degradation of haem to biliverdin, carbon monoxide and iron. There is increasing evidence that HO plays important roles in the cellular defence against oxidative stress and the deleterious effects of pro-inflammatory cytokines. In the present study, we investigated the effects of lipopolysaccharide (LPS) on the expression of HO-I in mouse placenta. When a single dose of LPS (75 mu g/kg, i.p.) was administered to the pregnant mice, the expression of HO-1 in mouse placenta was markedly increased at 12 h after LPS treatment and remained elevated up to 48 It after LPS administration. The expression of HO-2, the constitutive form, did not change at the various time points observed. LPS-induced up-regulation of placental HO-1 was blocked after the pregnant mice were pre-treated with alpha-phenyl-N-t-butylnitrone (PBN), a free radical spin trapping agent. Correspondingly, PBN pre-treatment significantly inhibited LPS-induced lipid peroxidation and glutathione (GSH) depletion in mouse placenta. Furthermore, pentoxifylline (PTX), an inhibitor of tumour necrosis factor alpha (TNF-alpha) synthesis, also significantly attenuated LPS-induced up-regulation of placental HO-1. However, aminoguanidine (AG), a selective inhibitor of inducible nitric oxide synthase (NOS), had little effect on LPS-induced up-regulation of HO-1 in mouse placenta. Taken together, these results indicate that LPS up-regulates the expression of HO-1 in mouse placenta. LPS-induced up-regulation of placental HO-1 is probably mediated, at least in part, by reactive oxygen species (ROS) and TNF-alpha, rather than nitric oxide. (c) 2007 Published by Elsevier Ltd.