FACTORS INVOLVED IN THE DOWN-REGULATION OF CYTOCHROME-P450 DURING LISTERIA-MONOCYTOGENES INFECTION
FACTORS INVOLVED IN THE DOWN-REGULATION OF CYTOCHROME-P450 DURING LISTERIA-MONOCYTOGENES INFECTION
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DOI：
10.1016/0192-0561(94)90094-9
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发表时间：
1994-09-01
期刊：
影响因子：
--
通讯作者：
RENTON, KW
中科院分区：
文献类型：
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作者：
ARMSTRONG, SG;RENTON, KW
宿主防御机制的激活已被证明会导致啮齿动物和人类肝脏细胞色素P450介导的代谢抑制。在以前的研究中，它被证明，革兰氏阳性细菌单核细胞增生李斯特菌导致下调肝细胞色素P450和相关的底物代谢作为一个翻译前抑制载脂蛋白合成的结果。本研究的目的是，以确定是否对肝细胞色素P450的影响，包括肝非实质细胞和是否溶血素，分泌的溶血形式的细菌，发挥任何部分在介导这种效果。总细胞色素P450水平以及乙氧基试卤灵-O-脱烷基酶（EROD（+））和苄氧基试卤灵-O-脱烷基酶（BROD）的活动显着降低，而相同剂量的无毒非溶血性M3 D菌株在体内感染48小时的小鼠分离的肝微粒体中没有影响。李斯特菌（15 U）显着抑制肝细胞EROD和BROD活动后，24小时的肝细胞培养物中含有肝细胞和非实质细胞，作为一个结果，对肝细胞的直接影响和相互作用的李斯特菌与肝非实质细胞。在分离的细胞中，M3 D菌株对细胞色素P-450介导的代谢没有影响，这证实了溶血素是负责细胞色素P450在Escherichia感染过程中下调的机制的重要组成部分。
The activation of host defense mechanisms has been shown to cause a depression in hepatic cytochrome P450-mediated metabolism in rodents and humans. In a previous study, it was demonstrated that the Gram-positive bacteria Listeria monocytogenes causes a down-regulation of hepatic cytochrome P450 and related substrate metabolism as a result of a pretranslational depression of apoprotein synthesis. The objectives of this study were to determine whether the effect of listeria on hepatocyte cytochrome P450 involves hepatic nonparenchymal cells and whether the hemolysin, secreted only by hemolytic forms of the bacteria, plays any part in mediating this effect. Total cytochrome P450 levels as well as ethoxyresorufin-O-dealkylase (EROD(+)) and benzyloxyresorufin-O-dealkylase (BROD) activities were significantly reduced in hepatic microsomes isolated from mice infected in vivo for 48 h with 15U listeria, whereas the same dose of the avirulent non-hemolytic M3D strain had no effect. Listeria (15U) significantly depressed hepatocyte EROD and BROD activities after 24 h incubations with liver cell cultures containing hepatocytes and nonparenchymal cells, as the result of both a direct effect on the hepatocyte and an interaction of listeria with hepatic nonparenchymal cells. The M3D strain of listeria had no effect on cytochrome P-450-mediated metabolism in isolated cells, confirming that hemolysin is an essential component of the mechanism responsible for the down-regulation of cytochrome P450 during listeria infections.