Lack of PPARα exacerbates lipopolysaccharide-induced liver toxicity through STAT1 inflammatory signaling and increased oxidative/nitrosative stress.
Lack of PPARα exacerbates lipopolysaccharide-induced liver toxicity through STAT1 inflammatory signaling and increased oxidative/nitrosative stress.
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DOI：
10.1016/j.toxlet.2011.01.013
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发表时间：
2011-04-10
影响因子：
3.5
通讯作者：
Song, Byoung-Joon
中科院分区：
文献类型：
--
作者：
Yoo, Seong Ho;Park, Ogyi;Henderson, Lauren E.;Abdelmegeed, Mohamed A.;Moon, Kwan-Hoon;Song, Byoung-Joon
过氧化物酶体增殖物激活受体-α (PPARα)具有有效的抗炎活性。然而，在急性肝损伤中，PPARα是否会影响信号转导和转录蛋白激活因子（STATs）尚无相关信息。因此，本研究旨在探讨PPARα在脂多糖（LPS）诱导的急性肝脏炎症损伤模型中升高STATs和氧化/亚硝化应激的体内作用。使用年龄匹配的ppara缺失和野生型（WT）小鼠，我们证明ppara缺失通过激活STAT1和NF-κB-p65，伴随着促炎细胞因子水平的增加，加重了lps介导的肝损伤。此外，与WT相比，暴露于lps的ppara缺失小鼠的关键抗氧化酶和线粒体复合物活性显著降低，脂质过氧化和蛋白质硝化水平升高。这些结果表明，PPARα通过调节STAT1炎症信号通路和氧化/亚硝化应激，在预防lps诱导的急性肝损伤中发挥重要作用。
Peroxisome proliferator-activated receptor-α (PPARα) has been implicated in a potent anti-inflammatory activity. However, no information is available on whether PPARα can affect signal transducers and activator of transcription proteins (STATs) in acute liver damage. Thus, this study was aimed to investigate the in vivo role of PPARα in elevating STATs as well as oxidative/nitrosative stress in a model of lipopolysaccharide (LPS)-induced acute hepatic inflammatory injury. Using age-matched Ppara-null and wild-type (WT) mice, we demonstrate that the deletion of PPARα aggravates LPS-mediated liver injury through activating STAT1 and NF-κB-p65 accompanied by increased levels of pro-inflammatory cytokines. Furthermore, the activities of key anti-oxidant enzymes and mitochondrial complexes were significantly decreased while lipid peroxidation and protein nitration were elevated in LPS-exposed Ppara-null mice compared to WT. These results indicate that PPARα is important in preventing LPS-induced acute liver damage by regulating STAT1 inflammatory signaling pathways and oxidative/nitrosative stress.
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影响因子：
4
作者：
Delerive, P;Fruchart, JC;Staels, B
通讯作者：
Staels, B
影响因子：
7.4
作者：
Abdelmegeed, Mohamed A.;Moon, Kwan-Hoon;Hardwick, James P.;Gonzalez, Frank J.;Song, Byoung-Joon
通讯作者：
Song, Byoung-Joon
影响因子：
3.1
作者：
Di Paola, Rosanna;Esposito, Emanuela;Cuzzocrea, Salvatore
通讯作者：
Cuzzocrea, Salvatore
影响因子：
7.3
作者：
Leach, M;Frank, S;Thiemermann, C
通讯作者：
Thiemermann, C
影响因子：
13.5
作者：
Jaeschke, H;Ho, YS;Farhood, A
通讯作者：
Farhood, A