Estradiol stimulates apolipoprotein A-I- but not A-II-containing particle synthesis and secretion by stimulating mRNA transcription rate in Hep G2 cells

被引:22
作者
Jin, FY
Kamanna, VS
Kashyap, ML
机构
[1] Dept Vet Affairs Med Ctr, Gerontol Sect 111GE, Ctr Cholesterol, Med Serv, Long Beach, CA 90822 USA
[2] Univ Calif Irvine, Irvine, CA 92717 USA
关键词
estrogen; high density lipoproteins; apolipoprotein A-I; cardiovascular disease;
D O I
10.1161/01.ATV.18.6.999
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Estrogen therapy increases plasma HDL levels, which may reduce cardiovascular risk in postmenopausal women. The mechanism of action of estrogen in influencing various steps in hepatic HDL and apolipoprotein (apo) A-I synthesis and secretion are not fully understood. In this study, we have used the human hepatoblastoma cell line (Hep G2) as an in vitro model system to delineate the effect of estradiol on multiple regulatory steps involved in hepatic HDL metabolism. Incubation of Hep G2 cells with estradiol resulted in the following statistically significant findings: (1) increased accumulation of apoA-I in the medium without affecting uptake/removal of radiolabeled HDL-protein; (2) accelerated incorporation of [H-3]leucine into apoA-I; (3) selective increase in [H-3]leucine incorporation into lipoprotein (LP) A-I but not LP A-I+A-II HDL particles (HDL particles without and with apoA-II, respectively); (4) increased ability of apoA-I-containing particles to efflux cholesterol from fibroblasts; (5) stimulated steady state apoA-I but not apoA-II mRNA expression; and (6) increased newly transcribed apoA-I mRNA message without effect on apoA-I mRNA half-life. The data indicate that estradiol stimulates newly transcribed hepatic apoA-I mRNA, resulting in a selective increase in LP A-I, a subfraction of HDL that is associated with decreased atherosclerotic cardiovascular disease, especially in premenopausal women.
引用
收藏
页码:999 / 1006
页数:8
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