Elimination and active extrusion of livermitochondrial proteins during LPS administration in rat
Elimination and active extrusion of livermitochondrial proteins during LPS administration in rat
复制标题
大鼠 LPS 给药过程中肝线粒体蛋白的消除和主动挤出
DOI：
10.1111/j.1872-034x.2012.01084.x
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Koichi Uemura
中科院分区：
文献类型：
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作者：
Kana Unuma;Toshihiko Aki;Seiji Matsuda;Takeshi Funakoshi;Ken-ichi Yoshida;Koichi Uemura
目的本研究的目的是确定在脂多糖（LPS）treatment.MethodsLPS（15 mg/kg体重）或车辆i. p.注射到5周龄雄性SD大鼠肝损伤的分子标志物。从肝脏中提取蛋白质，并进行酶切以检查LPS处理期间蛋白质组成的变化。使用蛋白质组学的方法，主要的LPS-在肝脏负责的蛋白determined.ResultsA的水平大幅减少氨基甲酰磷酸合酶-1（CPS 1），在肝脏线粒体中最丰富的蛋白质之一，揭示在LPS管理。电子显微镜和免疫荧光分析显示，在LPS处理的大鼠肝脏中，大空泡通常位于线粒体附近。此外，我们发现CPS 1在肝损伤标志物丙氨酸氨基转移酶之前被释放到循环中，表明LPS施用期间CPS 1的主动挤出。另一种肝线粒体蛋白，鸟氨酸转氨甲酰酶，也被释放到循环中，涉及线粒体蛋白的主动挤出。这些现象加速血红素加氧酶诱导剂钴原卟啉，而抑制了溶酶体抑制剂chloroquine.ConclusionPlasma CPS 1应该是一个可能的标志物脓毒性肝损伤，并可能参与全身反应引起的脓毒性休克。
AimThe purpose of the present study was to identify molecular markers of hepatic damage during lipopolysaccharide (LPS) treatment.MethodsLPS (15 mg/kg of bodyweight) or vehicle was injected i.p. into 5‐week‐old male Sprague–Dawley rats. Proteins were extracted from the liver and were electrophoresed to examine the changes in the protein compositions during LPS treatment. Using a proteomic approach, major LPS‐responsible protein in the liver was determined.ResultsA massive reduction in the levels of carbamoyl phosphate synthase‐1 (CPS1), one of the most abundant proteins in liver mitochondria, was revealed during LPS administration. Electron microscopic and immunofluorescence analyses revealed large vacuoles, which were often localized in the vicinity of mitochondria, in the LPS‐treated rat liver. Furthermore, we found that CPS1 is released into the circulation prior to liver damage marker alanine aminotransferase, indicating the active extrusion of CPS1 during LPS administration. Another liver mitochondrial protein, ornithine transcarbamylase, is also released into the circulation, implicating active extrusion of mitochondrial proteins. These phenomena are accelerated by a heme oxygenase inducer cobalt protoporphyrin whilst suppressed by a lysosome inhibitor chloroquine.ConclusionPlasma CPS1 should be a possible marker of septic liver damage and may be involved in systemic responses elicited by septic shock.