HCV proteins increase expression of heme oxygenase-1 (HO-1) and decrease expression of Bach1 in human hepatoma cells
HCV proteins increase expression of heme oxygenase-1 (HO-1) and decrease expression of Bach1 in human hepatoma cells
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DOI：
10.1016/j.jhep.2005.12.020
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发表时间：
2006-07-01
影响因子：
25.7
通讯作者：
Bonkovsky, Herbert L.
中科院分区：
文献类型：
--
作者：
Ghaziani, Tahereh;Shan, Ying;Bonkovsky, Herbert L.
背景/目的：丙型肝炎感染可导致肝脏氧化应激。血红素加氧酶(HO)是血红素分解代谢的速率控制酶，在抗氧化等应激反应中起着重要的保护作用。最近的其他工作还发现，抑制基因表达的血红素结合蛋白Bach1参与了HO-1基因表达的调控。方法：我们研究了丙型肝炎病毒多蛋白表达对人肝癌细胞(Huh-7细胞)HO-1和Bach1基因表达的影响。结果：HO-1在表达丙型肝炎病毒蛋白的细胞系中上调，从核心到NS3的氨基末端区域。随着N-乙酰半胱氨酸(NAC)浓度的增加，HO-1在表达丙型肝炎病毒蛋白的细胞中表达下调。相比之下，Bach1在这些细胞中的表达显著下调。氧化应激和HO-1的强诱导剂亚砷酸钠可降低野生型Huh-7细胞中Bach1的表达，NAC可部分抑制其表达。结论：表达丙型肝炎病毒的HH-7细胞中HO-1基因表达显著上调，而Bach1基因的表达相对下调。外源氧化应激源和抗氧化剂可以调节这些基因的表达。这些和其他结果表明，下调Bach1和上调HO-1在减弱丙型肝炎病毒蛋白对人肝细胞的细胞毒作用中起着关键作用。(C)2006年欧洲肝脏研究协会。爱思唯尔出版，版权所有。
Background/Aims: Hepatitis C infection induces hepatic oxidative stress. Heme oxygenase (HO), the rate-controlling enzyme of heme catabolism, plays a key role as a protector against oxidative, and other stresses. Other recent work has implicated Bach1, a heme binding protein that represses gene expression, in the regulation of HO-1 gene expression.Methods: We investigated the effects of HCV polyprotein expression on expression of HO-1 and Bach1 genes in human hepatoma cells (Huh-7 cells).Results: HO-1 was up-regulated in the cell line expressing HCV proteins from core up to the aminoterminal domain of NS3. Addition of increasing concentrations of N-acetyleysteine (NAC) led to down-regulation of HO-1 in cells expressing HCV proteins. In contrast, Bach1 was significantly down-regulated in these cells. Sodium arsenite, a strong inducer of oxidative stress and HO-1, reduced Bach1 expression in wild type Huh-7 cells, and NAC partially abrogated this decrease.Conclusions: Huh-7 cells expressing HCV proteins show significant up-regulation of the HO-1 gene, and reciprocal down-regulation of the Bach1 gene. Exogenous oxidative stressors and anti-oxidants can modulate expression of these genes. These and other results suggest a key role of down-regulation of Bach1 and up-regulation of HO-1 in diminishing cytotoxic effects of HCV proteins in human hepatocytes. (c) 2006 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.