Regulation of human apolipoprotein A-I gene expression by equine estrogens

Journal of Lipid Research

Jei-Jun Jiao¹  Bhagu R. Bhavnani²  Xia Zhang³  Shui-Pang Tam⁴ 

[1] Cancer Research Laboratories, Queen's University, Kingston, Ontario, Canada;Cancer Research Laboratories, Queen's University, Kingston, Ontario, Canada;Department of Biochemistry, Queen's University, Kingston, Ontario, Canada;Department of Obstetrics and Gynecology, Institute of Medical Sciences, University of Toronto and St. Michael's Hospital, Toronto, Ontario, Canada;

关键词: apolipoprotein A-I;    estrogen replacement therapy;    gene regulation;    HDL;   

DOI  :  

来源: DOAJ

【 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.

【 授权许可】

Unknown