Hepatitis B virus X protein promotes liver cell proliferation via a positive cascade loop involving arachidonic acid metabolism and p-ERK1/2
Hepatitis B virus X protein promotes liver cell proliferation via a positive cascade loop involving arachidonic acid metabolism and p-ERK1/2
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DOI：
10.1038/cr.2010.49
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发表时间：
2010-05-01
期刊：
影响因子：
44.1
通讯作者：
Zhang, Xiaodong
中科院分区：
文献类型：
--
作者：
Shan, Changliang;Xu, Fuqing;Zhang, Xiaodong
B型肝炎病毒X蛋白（HBx）在肝细胞癌的发生发展中起重要作用。在这里，我们试图确定HBx介导肝细胞增殖的机制。我们发现HBx上调肝细胞中环氧合酶-2（考克斯-2）、5-脂氧合酶（5-LOX）和磷酸化细胞外信号调节蛋白激酶1/2（p-ERK 1/2）的水平。抑制Gi/o蛋白、考克斯或LOX可消除HBx诱导的p-ERK 1/2。此外，HBx增加了从肝细胞衍生的细胞系释放的前列腺素E2（PGE 2）和白三烯B4（LTB 4）的量。此外，这些释放的花生四烯酸代谢产物能够激活ERK 1/2。ERK 1/2激活后可正反馈上调考克斯-2和5-LOX的表达。总之，HBx通过涉及考克斯-2，5-LOX、释放的花生四烯酸代谢物、Gi/o蛋白和p-ERK 1/2的正反馈环来增强和维持肝细胞增殖。
Hepatitis B virus X protein (HBx) plays a crucial role in the development of hepatocellular carcinoma. Here, we sought to identify the mechanisms by which HBx mediates liver cell proliferation. We found that HBx upregulated the levels of cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX) and phosphorylated extracellular signal-regulated protein kinases 1/2 (p-ERK1/2) in liver cells. HBx-induced p-ERK1/2 was abolished by inhibition of Gi/o proteins, COX or LOX. In addition, HBx increased the amounts of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) released from cell lines derived from hepatocytes. Moreover, these released arachidonic acid metabolites were able to activate ERK1/2. Interestingly, activated ERK1/2 could upregulate the expression of COX-2 and 5-LOX in a positive feedback manner. In conclusion, HBx enhances and maintains liver cell proliferation via a positive feedback loop involving COX-2, 5-LOX, released arachidonic acid metabolites, Gi/o proteins and p-ERK1/2.