Time-dependent effects of systemic lipopolysaccharide injection on regulators of antioxidant defence Nrf2 and PGC-1α in the neonatal rat brain.
Time-dependent effects of systemic lipopolysaccharide injection on regulators of antioxidant defence Nrf2 and PGC-1α in the neonatal rat brain.
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DOI：
10.1159/000347161
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发表时间：
2013
影响因子：
2.4
通讯作者：
Sandberg M
中科院分区：
文献类型：
--
作者：
Correa F;Ljunggren E;Patil J;Wang X;Hagberg H;Mallard C;Sandberg M
兴奋性毒性和神经炎症都与氧化应激有关。一个转录因子Nrf 2和一个转录辅因子PGC-1α增加内源性抗氧化防御，从而可以调节神经元细胞死亡。在这里，我们研究了全身（i. p.）脂多糖（LPS）对脑Nrf 2和PGC-1α系统的影响。给7日龄大鼠幼仔注射LPS（0.3 mg/kg）。24 h后，γGCL-M、γGCL-C、Nrf 2、PGC-1α和MnSOD蛋白水平升高，而Keap 1水平降低。这些作用与磷酸化Akt水平的增加和组蛋白4乙酰化水平的升高相关。与此相反，72小时后LPS的Nrf 2系统的组件中的减少与Keap 1的增加平行观察。72 h后下调与p38 MAPK磷酸化有关，而PGC-1α和MnSOD蛋白水平及组蛋白乙酰化/甲基化模式无变化。新生大鼠全身性LPS诱导脑Nrf 2和PGC-1α的时间依赖性变化，这与早期报道的全身性LPS 24 h后观察到的保护作用（预处理）和72 h后观察到的有害作用（致敏）密切相关。总的来说，结果表明Nrf 2和PGC-1α是这些效应背后的可能机制。
Both excitotoxicity and neuroinflammation are associated with oxidative stress. One transcription factor, Nrf2 and one transcription co-factor PGC-1α, increase the endogenous antioxidant defense and can thus modulate neuronal cell death. Here we have investigated the temporal effects (24 and 72 h) of systemic (i.p.) administration of lipopolysaccharide (LPS) on the cerebral Nrf2 and PGC-1α systems. Seven-day old rat pups were injected with LPS (0.3 mg/kg). After 24 h the protein levels of γGCL-M, γGCL-C, Nrf2, PGC-1α and MnSOD were increased in parallel with decreased levels of Keap1. These effects were correlated with increased level of phosphorylated Akt and elevated acetylation of histone 4. In contrast, 72 h following LPS a decrease in the components of the Nrf2 system in parallel with an increase of Keap1 was observed. The down-regulation after 72 h correlated with phosphorylation of p38 MAPK, while there were no changes in PGC-1α and MnSOD protein levels or the acetylation/methylation pattern of histones. Systemic LPS in neonatal rats induced time dependent changes in brain Nrf2 and PGC-1α that correlated well with the protective effect observed after 24 h (preconditioning) and the deleterious effects observed after 72 h (sensitizing) of systemic LPS reported earlier. Collectively, the results point towards Nrf2 and PGC-1α as a possible mechanism behind these effects.
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影响因子：
15.1
作者：
Frank-Cannon TC;Alto LT;McAlpine FE;Tansey MG
通讯作者：
Tansey MG
影响因子：
6.1
作者：
Correa, Fernando;Mallard, Carina;Nilsson, Michael;Sandberg, Mats
通讯作者：
Sandberg, Mats
DOI：
10.1097/00004647-200008000-00004
发表时间：
2000-08-01
影响因子：
6.3
作者：
Bordet, R;Deplanque, D;Dupuis, B
通讯作者：
Dupuis, B
影响因子：
4.3
作者：
Rahman, I;Gilmour, PS;MacNee, W
通讯作者：
MacNee, W
姜黄素上调转录因子 Nrf2、HO-1 表达并保护大鼠大脑免受局灶性缺血
影响因子：
2.9
作者：
Yang, Chenhui;Zhang, Xiangjian;Liu, Ying
通讯作者：
Liu, Ying