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标题：Transcription factors and age-related decline in apolipoprotein A-I expression
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作者：Takaaki Nakamura ; Alison Fox-Robichaud ; Ryuichi Kikkawa 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：1999
卷号：40
期号：9
页码：1709-1718
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：Apolipoprotein (apo)A-I alone or as a component of high density lipoprotein particles has antiatherogenic properties. The age-dependent decline in abundance of this protein may underlie the higher risk for developing occlusive coronary artery disease (CAD) in older individuals. Similar to humans, expression of rat apoA-I also declines with age. Results in rats showed that levels of serum apoA-I protein, hepatic mRNA, and transcription of the gene were decreased to 39%, 18%, and 38%, respectively, in 180-day-old animals compared to those of newborn rats. These findings suggest that a nuclear mechanism(s) may account for the decline in apoA-I expression. Accordingly, we examined hepatic nuclear binding activity to four specific cis -acting elements of the rat apoA-I promoter. There were age-dependent changes of binding activity to two proximal sites, B and C, but not to the more distal elements, IRCE and A. Decreased B-site binding activity correlated with lower mRNA levels encoding the activator, HNF-3β. The age-dependent change in the pattern of binding to site C was due to a switch from the activator, HNF-4, to the repressor, ARP-1. In summary, the age-related decline in apoA-I expression may arise from a reduction in the activity of both cis-acting elements, B and C. —Nakamura, T., A. Fox-Robichaud, R. Kikkawa, A. Kashiwagi, H. Kojima, M. Fujimiya, and N. C. W. Wong. Transcription factors and age-related decline in apolipoprotein A-I expression. J. Lipid Res. 1999. 40: 1709–1718.
关键词：aging ; atherosclerosis ; HNF-3 ; HNF-4 ; ARP-1 ; lipoprotein ; cholesterol ; HDL