文章基本信息

标题：Regulation of human apolipoprotein A-I gene expression by equine estrogens
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作者：Xia Zhang ; Jei-Jun Jiao ; Bhagu R. Bhavnani 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2001
卷号：42
期号：11
页码：1789-1800
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：Estrogen replacement therapies, such as conjugated equine estrogen (CEE, Premarin®), reduce the risk of coronary heart disease among postmenopausal women. In the present study, a HepG2 stable cell line (HepG2/S) that harbors a luciferase reporter gene cassette with the human apolipoprotein A-I (apoA-I) promoter region was used to examine the activity of CEE components in modulating human apoA-I promoter activity. A number of estrogens modulated apoA-I promoter activity, with equilenin (Eqn) being the most potent. Eqn produced a 3-fold increase in apoA-I promoter activity and a similar increase in apoA-I mRNA without affecting its degradation rate. Nuclear runoff assays indicated that the transcription rate of the apoA-I gene was increased 2.5-fold in Eqn-treated cells. When HepG2/S cells were exposed to Eqn, apoA-I protein secretion increased by 80%, whereas the level of secreted apoA-II remained unchanged. Transient transfection studies with human apoA-I promoter constructs derived from pGL3-luciferase reporter plasmid were used to identify the cis -acting element involved in Eqn-mediated induction. The results demonstrated that the apoA-I electrophile/antioxidant response element (EpRE/ARE) might be responsible for the increase in apoA-I promoter activity by Eqn. Cotransfection experiments using estrogen receptor (ERα and/or ERβ) expression vectors have indicated that neither receptor can potentiate the Eqn-mediated induction of apoA-I promoter activity. In addition, mobility shift analysis using antibody against either ERα or ERβ cannot detect the presence of these receptors in the DNA-protein complex. The data indicate that Eqn can induce the promoter activity of the human apoA-I gene, leading to an increase in apoA-I mRNA levels and apoA-I protein secretion through an ER-independent pathway involving apoA-I EpRE/ARE. —Zhang, X., J-J. Jiao, B. R. Bhavnani, and S-P. Tam. Regulation of human apolipoprotein A-I gene expression by equine estrogens. J. Lipid Res. 2001. 42: 1789–1800.
关键词：apolipoprotein A-I ; estrogen replacement therapy ; gene regulation ; HDL