Hepatitis C virus NS5A protein increases hepatic lipid accumulation via induction of activation and expression of PPARgamma

Hepatitis C virus NS5A protein increases hepatic lipid accumulation via induction of activation and expression of PPARgamma
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DOI:
10.1016/j.febslet.2009.07.034
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发表时间:
2009-09-03
期刊:
影响因子:
3.5
通讯作者:
Cheong, JaeHun
Cheong, JaeHun
中科院分区:
生物学3区
文献类型:
--
作者:
Kim, KyeongJin;Kim, Kook Hwan;Cheong, JaeHun

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脂肪变性是慢性丙型肝炎疾病进展的一个确定的危险因素。最近有研究表明,丙型肝炎病毒(HCV)核心和非结构(NS)2蛋白(NS2)可诱导肝细胞中的脂质积累。然而,尚不清楚其他HCV蛋白是否与脂质代谢有关。NS5A增强了PPAR γ的转录活性和基因表达。此外,NS5A增加了PPAR γ将转录辅激活子PGC-1募集到PPRE的能力,以及与PPAR γ 2和PGC-1 α的相互作用。我们的研究结果表明,NS5A可能利用多种策略增强PPAR γ诱导的脂质积累。结构摘要:MINT-7229685: PPAR伽玛2 (uniprotkb: P37231-2)物理相互作用(MI: 0914)与PGC1 α (uniprotkb: Q9UBK2)通过下拉(MI: 0096)MINT-7229712: PPAR伽玛2 (uniprotkb: P37231-2)物理相互作用(MI: 0914)与NS5A (uniprotkb: P26662)通过下拉(MI: 0096)MINT-7229698: PPAR伽玛2 (uniprotkb: P37231-2)物理相互作用(MI: 0914)通过抗标签共免疫沉淀(MI: 0007) PPAR伽玛2 (uniprotkb: Q9UBK2)通过抗标签共免疫沉淀(MI: 0007)P37231-2)通过抗标签共免疫沉淀(MI: 0007)与NS5A(单蛋白:P26662)物理相互作用(MI: 0914) (C) 2009年欧洲生化学会联合会。Elsevier b.v.版权所有。
Steatosis is an established risk factor for disease progression in cases of chronic hepatitis C. Recently it was demonstrated that Hepatitis C virus (HCV) core and non-structural (NS)2 proteins (NS2) induce lipid accumulation in hepatic cells. However, it has yet to be determined whether other HCV proteins are associated with lipid metabolism. The NS5A augmented the transcriptional activity and gene expression of PPAR gamma. Furthermore, NS5A increased the ability to recruit the transcriptional coactivator PGC-1s to the PPRE with PPAR gamma, as well as the interaction with PPAR gamma 2 and PGC-1 alpha. Our results indicate that NS5A may exploit multiple strategies that enhance PPAR gamma-induced lipid accumulation.Structured summary:MINT-7229685: PPAR gamma 2 (uniprotkb: P37231-2) physically interacts (MI: 0914) with PGC1 alpha (uniprotkb: Q9UBK2) by pull down (MI: 0096)MINT-7229712: PPAR gamma 2 (uniprotkb: P37231-2) physically interacts (MI: 0914) with NS5A (uniprotkb: P26662) by pull down ( MI: 0096)MINT-7229698: PPAR gamma 2 (uniprotkb: P37231-2) physically interacts (MI: 0914) with PGC1 alpha (uniprotkb: Q9UBK2) by anti tag coimmunoprecipitation ( MI: 0007)MINT-7229731: PPAR gamma 2 (uniprotkb: P37231-2) physically interacts (MI: 0914) with NS5A (uniprotkb: P26662) by anti tag coimmunoprecipitation (MI: 0007) (C) 2009 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.