Hepatocytes proteomic alteration and seroproteome analysis of HBV-transgenic mice
Hepatocytes proteomic alteration and seroproteome analysis of HBV-transgenic mice
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HBV转基因小鼠肝细胞蛋白质组改变和血清蛋白质组分析
DOI：
10.1002/pmic.200701053
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发表时间：
2009-01-01
期刊：
影响因子：
3.4
通讯作者：
Tian, Zhigang
中科院分区：
文献类型：
--
作者：
Ding, Chen;Wei, Haiming;Tian, Zhigang
乙型肝炎是最常见和最严重的肝脏疾病，特别是在发展中国家。虽然HBV的发病机制已被广泛研究，但HBV慢性感染期间肝细胞的蛋白质组学改变仍不清楚。利用纯化的肝细胞，我们用2-DE和LC-MS比较了hbv转基因（Tg）和相应背景小鼠的蛋白谱。在HBV-Tg小鼠肝细胞中鉴定出27个改变蛋白，其中13个蛋白参与线粒体代谢途径，包括三羧酸（TCA）循环和氧化反应；四种蛋白（SELENBP、SCP2、RGN和PRDX1）在hbv感染患者的肝脏样本中也发生了显著变化。HBV-Tg小鼠肝脏中与氧化损伤相关的重要基因（gpx、sod、ogg等）表达上调。HBV-Tg小鼠肝线粒体活性氧产生显著增加，ATP产生显著减少。此外，HBV-Tg小鼠的肝细胞对过氧化氢诱导的细胞死亡比野生型对照组更敏感。通过二维Western blotting分析，发现8种肝细胞蛋白与HBV-Tg小鼠血清发生反应，而与背景小鼠血清不发生反应。有趣的是，八种反应蛋白中的两种（Etfa和Dmgdh）在HBV-Tg小鼠中过表达。我们认为这项研究是首次对HBV感染的哺乳动物肝细胞进行蛋白质组学和血清蛋白质组学分析，并提供了HBV感染与HBV诱导的肝脏疾病之间的深刻联系。
Hepatitis B is the most common and serious liver disease, especially in developing countries. Although HBV pathogenesis has been extensively investigated, the proteomic alteration of hepatocytes during HBV chronic infection is still unclear. Using the purified hepatocytes, we compared the protein profiles by 2-DE and LC-MS between HBV-transgenic (Tg) and corresponding background mice. Twenty-seven altered proteins were identified in hepatocytes from HBV-Tg mice, among which 13 proteins were involved in mitochondrion metabolism pathway including tricarboxylic acid (TCA) cycle and oxidative response; four proteins (SELENBP, SCP2, RGN and PRDX1) were also dramatically changed in liver samples from HBV-infected patients. Important genes (gpx, sod, ogg et al.) correlated to oxidative damage were up-regulated in the liver of HBV-Tg mice. Reactive oxygen species production was significantly increased while ATP production was decreased in liver mitochondria from HBV-Tg mice. Moreover, hepatocytes of HBV-Tg mice were more sensitive to hydrogen peroxide-induced cell death than that of wild-type control. Using 2-D Western blotting analysis, eight hepatocyte proteins were found to react with sera of HBV-Tg mice but not with that of background mice. Interestingly, two (Etfa and Dmgdh) of the eight reactive proteins were overexpressed in HBV-Tg mice. We believe this study is the first proteomic and seroproteome analysis of HBV-infected mammalian hepatocyte and provides insightful links between HBV infection and HBV-induced liver diseases.