Geranylgeranylacetone induces antiviral gene expression in human hepatoma cells.

Geranylgeranylacetone induces antiviral gene expression in human hepatoma cells.
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香叶基香叶基丙酮诱导人肝癌细胞中的抗病毒基因表达。

DOI:
10.1006/bbrc.2000.4228
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发表时间:
2001
影响因子:
3.1
通讯作者:
K. Eguchi
K. Eguchi
中科院分区:
生物学4区
文献类型:
--
作者:
T. Ichikawa;K. Nakao;K. Nakata;K. Hamasaki;Y. Takeda;Y. Kajiya;S. Higashi;K. Ohkubo;Y. Kato;N. Ishii;K. Eguchi

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香叶基香叶基丙酮(GGA)是一种类异戊二烯化合物,临床上用作抗溃疡药物。由于包括类维生素A在内的一些类异戊二烯在多种细胞类型中具有抗肿瘤和抗病毒活性,我们研究了GGA是否可以在人肝癌细胞中诱导抗病毒蛋白。用GGA处理HuH-7和HepG 2细胞,并分析这些细胞中抗病毒蛋白如2 '5'-寡腺苷酸合成酶(2 '5'-OAS)和双链RNA依赖性蛋白激酶(PKR)的表达。GGA通过形成干扰素刺激基因因子3(ISGF 3)在转录水平刺激2 '5'-OAS和PKR基因表达,ISGF 3调节这两个基因的转录。通过蛋白质印迹,GGA诱导信号转导和转录激活因子1,2(STAT 1,STAT 2)和p48蛋白,ISGF 3的组成部分的表达,连同STAT 1的磷酸化。这些结果表明,GGA作为一个有效的诱导剂的抗病毒基因表达刺激ISGF 3形成在人肝癌细胞。
Geranylgeranylacetone (GGA), an isoprenoid compound, is used clinically as an anti-ulcer drug. Since some isoprenoids including retinoids have anti-tumor and anti-viral activities in a variety of cell types, we investigated whether GGA could induce anti-viral proteins in human hepatoma cells. The HuH-7 and HepG2 cells were treated with GGA, and expression of anti-viral proteins such as 2'5'-oligoadenylate synthetase (2'5'-OAS) and double-stranded RNA-dependent protein kinase (PKR) in these cells was analyzed. GGA stimulated 2'5'-OAS and PKR gene expression at the transcriptional level through the formation of interferon-stimulated gene factor 3 (ISGF3), which regulates both gene transcription. By Western blotting, GGA induced expression of signal transducers and activators of transcription 1, 2 (STAT1, STAT2) and p48 proteins, components of ISGF3, together with the phosphorylation of STAT1. These results suggest that GGA acts as a potent inducer of anti-viral gene expression by stimulating the ISGF3 formation in human hepatoma cells.
DOI: 10.1016/s0016-5085(00)70134-x
发表时间: 2000-04-01
期刊: GASTROENTEROLOGY
影响因子: 29.4
作者:
Nelson, DR;Lauwers, GY;Davis, GL
通讯作者: Davis, GL
DOI: 10.1101/gad.2.4.383
发表时间: 1988-04-01
影响因子: 10.5
作者:
LEVY, DE;KESSLER, DS;DARNELL, JE
通讯作者: DARNELL, JE