Transcription factors and age-related decline in apolipoprotein A-I expression

Abstract

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-3 ␤ . 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

Proteomic profiling of archaeological human bone

“…Apolipoprotein A-1 (APOA1) is the major protein component of high density lipoprotein (HDL) in plasma. The expression level of APOA1 in blood has been reported to decrease with age [52,53]. In this study, APOA1 was detected only in the youngest infant (0.75 years old), which is consistent with the previous research [52,53].…”

Liver X Receptor Inhibits the Synthesis and Secretion of Apolipoprotein A1 by Human Liver-Derived Cells

“…Effects of COUP-TF Proteins on Apo A1. COUP-TF family proteins, by displacing HNF-family proteins from their proximal promoter sites, are major regulators of apo A1 transcription in vivo and in vitro ( , ). To determine if changes in COUP levels mediated the effects of TO901317, total COUP-TF was first assayed in Hep3B cells by Western blotting in the presence and absence of the ligand, using an antibody detecting both COUP-TF1 and COUP-TF2.…”

“…HNF proteins react as homodimers with direct repeats (DRs) based on a regulatory sequence (AGGTCA) separated by a single nucleotide. A second family of transcription factors, chicken ovalbumin upstream promoter transcription factors (COUP-TFs), inhibits apo A1 transcription competitively ( , ). Two closely related proteins, COUP-TFI and COUP-TFII, are expressed in liver cells.…”

ProteinChip Technology: A New and Facile Method for the Identification and Measurement of High-Density Lipoproteins apoA-I and apoA-II and Their Glycosylated Products in Patients with Diabetes and Cardiovascular Disease

“…Many but not all epidemiological studies have indicated a closer association of HDL apolipoprotein A-I with heart disease risk than with HDL-C. [4][5][6][7][8] ApoA-II associated with HDL2 does not seem to have a similar protective effect. 4,[7][8][9] In patients with diabetes, glycosylation of HDL may result in a functionally abnormal and atherogenic apolipoprotein A-I particle. [10][11][12][13] Traditionally, protein expression levels in plasma samples have been compared using one-dimensional or two-dimensional (1D and 2D) gel electrophoresis.…”

“…Plasma high-density lipoprotein cholesterol (HDL-C) levels are inversely correlated with risk for atherosclerosis. − The mechanism(s) for this association may involve reverse transport of cholesterol. Many but not all epidemiological studies have indicated a closer association of HDL apolipoprotein A-I with heart disease risk than with HDL-C. − ApoA-II associated with HDL 2 does not seem to have a similar protective effect. ,− In patients with diabetes, glycosylation of HDL may result in a functionally abnormal and atherogenic apolipoprotein A-I particle. − …”