...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Shock: Molecular, cellular, and systemic pathobiological aspects and therapeutic approaches = The official journal of the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies >Farnesyltransferase inhibitor, tipifarnib, prevents galactosamine/lipopolysaccharide-induced acute liver failure.
【24h】

Farnesyltransferase inhibitor, tipifarnib, prevents galactosamine/lipopolysaccharide-induced acute liver failure.

机译：tipifarnib批抑制剂,防止半乳糖胺/ lipopolysaccharide-induced急性肝衰竭。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Acute liver failure (ALF) is a fatal syndrome associated with massive hepatocyte death. There is no cure for ALF except liver transplantation. Protein farnesylation is a lipid modification of cysteine residues that is catalyzed by farnesyltransferase (FTase) and has been proposed as an integral component of acute inflammation. Previously, we have demonstrated that FTase inhibitors improve survival in mouse models of endotoxemia and sepsis. Here we studied the effects of FTase inhibitor, tipifarnib, on galactosamine (GalN)/lipopolysaccharide (LPS)-induced ALF. The effects of tipifarnib (10 mg/kg, i.p.) were studied in GalN (400 mg/kg, i.p.)- and LPS (3 μg/kg)-challenged mice by histological and biochemical analyses. Galactosamine/LPS administration caused prominent liver injury characterized by the increased plasma alanine aminotransferase and aspartic aminotransferase levels, leading to significant mortality in mice. Tipifarnib inhibited GalN/LPS-induced caspase 3 activation, inflammatory cytokine production, and c-Jun N-terminal kinase phosphorylation in the liver. On the other hand, tipifarnib upregulated antiapoptotic protein, Bcl-xL, in the liver after GalN/LPS challenge. Tipifarnib also protected primary hepatocytes from GalN/tumor necrosis factor α-induced cell death by inhibiting caspase 3 activation and upregulating antiapoptotic proteins. Galactosamine/LPS-induced liver injury was associated with increased protein farnesylation in the liver. Tipifarnib prevented protein farnesylation in the liver and markedly attenuated liver injury and mortality in GalN/LPS-challenged mice. These results suggest that protein farnesylation is a novel potential molecular target to prevent hepatocyte death and acute inflammatory liver failure in fulminant hepatitis.
机译：急性肝功能衰竭(ALF)是一种致命的综合症与大量的肝细胞死亡有关。没有治愈阿尔夫除了肝移植。蛋白质farnesylation是脂类的修改半胱氨酸残基所催化治疗(简称ftis)和已经提出作为急性炎症的不可或缺的组成部分。以前,我们已经表明,简称ftis抑制剂改善生存的小鼠模型内毒素和败血症。tipifarnib,简称ftis抑制剂的影响半乳糖胺(GalN) /脂多糖(有限合伙人)全身的阿尔夫。毫克/公斤,i.p)。研究了在GalN(400毫克/公斤,i.p)和有限合伙人(3μg / kg)挑战老鼠组织学和生化分析。半乳糖胺/有限合伙人管理突出造成的肝损伤的增加血浆丙氨酸转氨酶和天冬氨酸的转氨酶水平,导致重大的小鼠的死亡率。GalN / LPS-induced半胱天冬酶3激活,炎性细胞因子的生产,c-Jun氨基端激酶磷酸化在肝脏。另一方面,tipifarnib调节凋亡蛋白(Bcl-xL,后在肝脏GalN /有限合伙人的挑战。主要从GalN /肿瘤坏死肝细胞抑制半胱天冬酶因子α全身的细胞死亡3激活和上调抗凋亡蛋白质。与蛋白质增加有关吗farnesylation在肝脏。蛋白质farnesylation在肝脏和明显减毒肝损伤和死亡GalN / LPS-challenged老鼠。蛋白质farnesylation是一种新型的潜力分子,防止肝细胞死亡和目标急性炎症在暴发性肝衰竭肝炎。

著录项

相似文献

  • 外文文献
  • 中文文献
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号