Hepatitis B Virus Induces Expression of Antioxidant Response Element-regulated Genes by Activation of Nrf2
Hepatitis B Virus Induces Expression of Antioxidant Response Element-regulated Genes by Activation of Nrf2
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DOI：
10.1074/jbc.m110.145862
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发表时间：
2010-12-24
影响因子：
4.8
通讯作者：
Hildt, Eberhard
中科院分区：
文献类型：
--
作者：
Schaedler, Stephanie;Krause, Janis;Hildt, Eberhard
多种细胞保护基因的表达受其启动子中的短顺式元件（称为抗氧化反应元件（AREs））的调控。are介导的基因表达的一个中心调节因子是nf - e2相关因子2 （Nrf2）。人乙型肝炎病毒（HBV）在体内和体外诱导Nrf2/ are调控基因的强烈激活。这是由hbv调节蛋白（HBx和LHBs）通过c-Raf和MEK触发的。与对照细胞相比，Nrf2/ are介导的HBV对细胞保护基因的诱导可以更好地保护HBV阳性细胞免受氧化损伤。此外，在hbv阳性细胞中，Nrf2/ are调节的蛋白酶体亚基PSMB5的表达显著增加，这与免疫蛋白酶体亚基PSMB5i水平降低有关。根据这一发现，即使在干扰素/ γ治疗后，hbv阳性细胞与对照细胞相比，表现出更高的组成蛋白酶体活性和更低的免疫蛋白酶体活性。Nrf2/ are调节基因的HBV依赖性诱导可能确保感染细胞的存活，形成对HBV的免疫反应，从而促进感染的建立。
The expression of a variety of cytoprotective genes is regulated by short cis-acting elements in their promoters, called antioxidant response elements (AREs). A central regulator of ARE-mediated gene expression is the NF-E2-related factor 2 (Nrf2). Human hepatitis B virus (HBV) induces a strong activation of Nrf2/ARE-regulated genes in vitro and in vivo. This is triggered by the HBV-regulatory proteins (HBx and LHBs) via c-Raf and MEK. The Nrf2/ARE-mediated induction of cytoprotective genes by HBV results in a better protection of HBV-positive cells against oxidative damage as compared with control cells. Furthermore, there is a significantly increased expression of the Nrf2/ARE-regulated proteasomal subunit PSMB5 in HBV-positive cells that is associated with a decreased level of the immunoproteasome subunit PSMB5i. In accordance with this finding, HBV-positive cells display a higher constitutive proteasome activity and a decreased activity of the immunoproteasome as compared with control cells even after interferon alpha/gamma treatment. The HBV-dependent induction of Nrf2/ARE-regulated genes might ensure survival of the infected cell, shape the immune response to HBV, and thereby promote establishment of the infection.