THE ROLES OF HEPATITIS C VIRUS AND INFLAMMATION IN THE PATHOGENESIS OF HEPATOCELLULAR CARCINOMA
丙型肝炎病毒和炎症在肝细胞癌发病机制中的作用
基本信息
- 批准号:13470115
- 负责人:
- 金额:$ 7.68万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (B)
- 财政年份:2001
- 资助国家:日本
- 起止时间:2001 至 2002
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
The mechanism of hepatocarcinogenesis in hepatitis C virus (HCV) infection is still undefined. One possibility is the involvement of oxidative stress, which can produce genetic mutations as well as gross chromosomal alterations and contribute to cancer development. We recently showed that the core protein of HCV induces, after a long period, hepatocellular carcinoma (HCC) in transgenic mice with marked hepatic steatosis but without inflammation, indicating a direct involvement of HCV in hepatocarcinogenesis. PCOOH level was increased by 180% in old core gene transgenic mice aged over 16 months. Concurrently, there was a significant increase in the catalase activity, and decreases in the levels of total and reduced glutathione in the same mice. Interestingly, alcohol caused a marked increase in PCOOH level in transgenic mice, suggesting synergism between alcohol and HCV in hepatocarcinogenesis. The HCV core protein thus afters the oxidant/antioxidant state in the liver in the absence of … More inflammation, and thereby may contribute to or facilitate, at least partly, the development of HCC in HCV infection. Since previous studies indicated that ROS is closely associated with mitogen-activated protein kinases (MAPK), we examined activities of c-Jun N-terminal kinase, p38 MAPK, and extracellular signal-regulated kinase (ERK) in the liver of core-transgenic and nontransgenic mice with short-term ethanol feeding. Activity of ERK and p38 MAPK was increased in core-transgenic mice compared with nontransgenic mice, whereas neither ERK nor p38 MAPK was activated hi core-transgenic mice with normal diets. In addition, activity of cyclic-AMP and serum responsive element, downstream pathways of p38 MAPK and ERK, was also increased. Comparison of gene expression profiles by cDNA microarray and real-time PCR revealed that galectin-1, which is associated with cell transformation, was significantly increased in ethanol-fed core-transgenic mice. On the other hand, glutathione S-transferase, which plays a key role in protecting cells from oxidative stress, was decreased. In conclusion, these results suggest that HCV core protein cooperates with ethanol for the activation of some MAPK pathways, and leads to the modulation of several genes, contributing to pathogenesis observed in livers of HCV-infected patients with high ethanol consumption. Less
丙型肝炎病毒(HCV)感染引起肝癌的机制尚不清楚。一种可能性是氧化应激的参与,它可以产生基因突变以及染色体的总体改变,并有助于癌症的发展。我们最近发现,丙型肝炎病毒的核心蛋白诱导,经过很长一段时间,肝细胞癌(HCC)的转基因小鼠有显着的肝脂肪变性,但没有炎症,表明直接参与丙型肝炎病毒在肝癌发生。在年龄超过16个月的老年核心基因转基因小鼠中,PCOH水平增加了180%。同时,在相同的小鼠中,过氧化氢酶活性显著增加,总谷胱甘肽和还原型谷胱甘肽水平降低。有趣的是,酒精引起转基因小鼠PCOH水平显着增加,表明酒精和HCV之间的协同作用,在肝癌发生。因此,HCV核心蛋白在肝脏中的氧化剂/抗氧化剂状态之后, ...更多信息 在HCV感染中,肝细胞癌的发生可能与炎症有关,从而可能至少部分地促成或促进HCC的发展。由于以往的研究表明,活性氧是密切相关的丝裂原活化蛋白激酶(MAPK),我们检查的c-Jun N-末端激酶,p38 MAPK,和细胞外信号调节激酶(ERK)在核心转基因和非转基因小鼠肝脏短期乙醇喂养的活动。与非转基因小鼠相比,核心转基因小鼠的ERK和p38 MAPK活性增加,而在正常饮食的核心转基因小鼠中ERK和p38 MAPK均未被激活。此外,p38 MAPK和ERK下游通路cyclic-AMP和血清反应元件的活性也增加。通过cDNA微阵列和实时PCR比较基因表达谱发现,与细胞转化相关的半乳糖凝集素-1在乙醇喂养的核心转基因小鼠中显著增加。另一方面,在保护细胞免受氧化应激中起关键作用的谷胱甘肽S-转移酶减少。总之,这些结果表明,HCV核心蛋白与乙醇合作激活一些MAPK途径,并导致几个基因的调制,有助于观察到的高酒精消耗的HCV感染患者的肝脏的发病机制。少
项目成果
期刊论文数量(48)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Koike K, Moriya K, Kimura S.: "Role of hepatitis C virus in the development of hepatocellular carcinoma : Transgenic approach to viral hepatocarcinogenesis"J Gastroenterol Hepatol. 17. 394-400 (2002)
Koike K、Moriya K、Kimura S.:“丙型肝炎病毒在肝细胞癌发展中的作用:病毒性肝癌发生的转基因方法”J Gastroenterol Hepatol。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Perlemuter G., et al.: "Hepatitis C virus core protein inhibits microsomal triglyceride transfer protein activity and very low density lipoprotein secretion: a model of viral-related steatosis"FASEB J. 16. 185-194 (2002)
Perlemuter G.等人:“丙型肝炎病毒核心蛋白抑制微粒体甘油三酯转移蛋白活性和极低密度脂蛋白分泌:病毒相关脂肪变性的模型”FASEB J. 16. 185-194 (2002)
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Tsutsumi T, et al.: "Alteration of intrahepatic cytokine expression and AP-1 activation in transgenic mice expressing hepatitis C core protein"Virology. 304. 415-424 (2002)
Tsutsumi T 等人:“表达丙型肝炎核心蛋白的转基因小鼠中肝内细胞因子表达和 AP-1 激活的改变”病毒学。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Koike K, et al.: "Role of hepatitis C virus in the development of hepatocellular carcinoma : Transgenic approach to viral hepatocarcinogenesis"J Gastroenterol Hepatol. 17. 394-400 (2002)
Koike K 等人:“丙型肝炎病毒在肝细胞癌发展中的作用:病毒性肝癌发生的转基因方法”J Gastroenterol Hepatol。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Moriya K, et al.: "Increase of carbon 18 mono-unsaturated fatty acids in the liver of hepatitis C : Analysis in transgenic mice and humans"Biophys Biochem Res Commun. 281. 1207-1212 (2001)
Moriya K 等人:“丙型肝炎肝脏中碳 18 单不饱和脂肪酸的增加:转基因小鼠和人类的分析”Biophys Biochem Res Commun。
- DOI:
- 发表时间:
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- 影响因子:0
- 作者:
- 通讯作者:
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KOIKE Kazuhiko其他文献
KOIKE Kazuhiko的其他文献
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{{ truncateString('KOIKE Kazuhiko', 18)}}的其他基金
Evaluation of environmental factors and the risks controlling ocean productivities at the coast of Myanmar
缅甸沿海环境因素及控制海洋生产力风险评估
- 批准号:
26304031 - 财政年份:2014
- 资助金额:
$ 7.68万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Expelled zooxanthellae from corals; possible source as symbionts to other corals
从珊瑚中排出虫黄藻;
- 批准号:
24570028 - 财政年份:2012
- 资助金额:
$ 7.68万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Development of hepatitis C virus suicide therapy employing the viral protease
利用病毒蛋白酶开发丙型肝炎病毒自杀疗法
- 批准号:
23659393 - 财政年份:2011
- 资助金额:
$ 7.68万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
Zooxanthellal cycle in coral reefs
珊瑚礁中的虫黄藻循环
- 批准号:
21310011 - 财政年份:2009
- 资助金额:
$ 7.68万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Metabolic abnormalities in hepatitis C and its impact on the progression of liver disease
丙型肝炎的代谢异常及其对肝病进展的影响
- 批准号:
20390204 - 财政年份:2008
- 资助金额:
$ 7.68万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Hepatitis C as a Metabolic Disease : Pathogenesis for liver cancer and lifestyle-related diseases
丙型肝炎作为一种代谢性疾病:肝癌和生活方式相关疾病的发病机制
- 批准号:
18390214 - 财政年份:2006
- 资助金额:
$ 7.68万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Study on representation theory of the classical groups and their related combinatorics
经典群表示论及其相关组合学研究
- 批准号:
18540046 - 财政年份:2006
- 资助金额:
$ 7.68万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Functional abnormality in the mitochondria and pathogenesis of chronic hepatitis C: relation to hepatocellular carcinoma
线粒体功能异常和慢性丙型肝炎的发病机制:与肝细胞癌的关系
- 批准号:
15390226 - 财政年份:2003
- 资助金额:
$ 7.68万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Representation Theory, Combinatorics and Related Topics
表示论、组合学及相关主题
- 批准号:
14540041 - 财政年份:2002
- 资助金额:
$ 7.68万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Study on the mechanism of hepatocarcinogenesis in hepatitis C viral infection
丙型肝炎病毒感染致肝癌机制研究
- 批准号:
13214018 - 财政年份:2001
- 资助金额:
$ 7.68万 - 项目类别:
Grant-in-Aid for Scientific Research on Priority Areas
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