scholarly journals Isoproterenol decreases LDL receptor expression in rat adipose cells: activation of cyclic AMP-dependent proteolysis

1996 ◽  
Vol 37 (2) ◽  
pp. 237-249
Author(s):  
F B Kraemer ◽  
V Natu ◽  
A Singh-Bist ◽  
S Patel ◽  
M C Komaromy ◽  
...  
Keyword(s):  
Cyclic Amp ◽  
Ldl Receptor ◽  
Receptor Expression ◽  
Adipose Cells

scholarly journals Agents which increase cyclic AMP have diverse effects on low-density-lipoprotein-receptor function in human vascular smooth-muscle cells and skin fibroblasts

1990 ◽  
Vol 267 (3) ◽  
pp. 607-614 ◽  
Author(s):  
A Middleton ◽  
B Middleton
Keyword(s):  
Smooth Muscle ◽  
Cyclic Amp ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Ldl Receptor ◽  
Muscle Cells ◽  
Skin Fibroblasts ◽  
Receptor Expression ◽  
Low Density

Receptor-mediated binding and metabolism of low-density lipoproteins (LDL) in cultured human vascular smooth-muscle cells and skin fibroblasts are altered by increased cellular cyclic AMP concentrations. However, the LDL receptor does not respond to changes in cyclic AMP concentration in a simple manner. The activation of adenylate cyclase with forskolin, or the addition of membrane-permeant cyclic AMP analogues, initially decreases the expression of the LDL receptor, but is followed by a substantial increase in receptor expression after 24 h. This increase does not occur in the presence of inhibitors of RNA or protein synthesis, and is due to doubling of the Bmax. of the LDL receptor, without alteration of its affinity for LDL. By contrast, elevation of cyclic AMP concentration by inhibition of phosphodiesterases results in decreased receptor expression throughout the 24 h period. These two response patterns are reproducible phenomena, consistently observed in low-passaged cells derived from seven unrelated individuals.

Sterol regulation of human LDL receptor expression in gene therapy

2000 ◽  
Vol 151 (1) ◽  
pp. 102-103
Author(s):  
J. Heeren ◽  
F. Schnieders ◽  
U. Beisiegel
Keyword(s):  
Gene Therapy ◽  
Ldl Receptor ◽  
Receptor Expression

Postprandial dyslipidemia in men with visceral obesity: an effect of reduced LDL receptor expression?

2001 ◽  
Vol 281 (3) ◽  
pp. E626-E632 ◽  
Author(s):  
John C. L. Mamo ◽  
Gerald F. Watts ◽  
P. Hugh R. Barrett ◽  
Darrin Smith ◽  
Anthony P. James ◽  
...  
Keyword(s):  
Plasma Cholesterol ◽  
Hydrolytic Enzyme ◽  
Ldl Receptor ◽  
Surrogate Marker ◽  
Visceral Obesity ◽  
Receptor Expression ◽  
Cell Protein ◽  
Insulin Resistant ◽  
Postprandial Triglyceride ◽  
Obese Subjects

Postprandial lipemia after an oral fat challenge was studied in middle-aged men with visceral obesity. The two groups had similar plasma cholesterol levels, but obese subjects had higher levels of plasma triglyceride and reduced amounts of high-density cholesterol. Fasting plasma insulin was fourfold greater in obese subjects because of concomitant insulin resistance, with a calculated HOMA score of 3.1 ± 0.6 vs. 0.8 ± 0.2, respectively. Plasma apolipoprotein B48(apoB48) and retinyl palmitate (RP) after an oral fat challenge were used to monitor chylomicron metabolism. Compared with lean subjects, the fasting concentration of apoB48 was more than twofold greater in obese individuals, suggestive of an accumulation of posthydrolyzed particles. After the oral lipid load, the incremental areas under the apoB48 and RP curves (IAUC) were both significantly greater in obese subjects (apoB48: 97 ± 17 vs. 44 ± 12 μg · ml−1 · h; RP: 3,120 ± 511 vs. 1,308 ± 177 U · ml−1 · h, respectively). A delay in the conversion of chylomicrons to remnants probably contributed to postprandial dyslipidemia in viscerally obese subjects. The triglyceride IAUC was 68% greater in obese subjects (4.7 ± 0.6 vs. 2.8 ± 0.8 mM · h, P< 0.06). Moreover, peak postprandial triglyceride was delayed by ∼2 h in obese subjects. The reduction in triglyceride lipolysis in vivo did not appear to reflect changes in hydrolytic enzyme activities. Postheparin plasma lipase rates were found to be similar for lean and obese subjects. In this study, low-density lipoprotein (LDL) receptor expression on monunuclear cells was used as a surrogate marker of hepatic activity. We found that, in obese subjects, the binding of LDL was reduced by one-half compared with lean controls (70.9 ± 15.07 vs. 38.9 ± 4.6 ng LDL bound/μg cell protein, P = 0.02). Because the LDL receptor is involved in the removal of proatherogenic chylomicron remnants, we suggest that the hepatic clearance of these particles might be compromised in insulin-resistant obese subjects. Premature and accelerated atherogenesis in viscerally obese, insulin-resistant subjects may in part reflect delayed clearance of postprandial lipoprotein remnants.

Flow cytometry with a monoclonal antibody to the low density lipoprotein receptor compared with gene mutation detection in diagnosis of heterozygous familial hypercholesterolemia

1998 ◽  
Vol 44 (5) ◽  
pp. 966-972 ◽  
Author(s):  
Bent Raungaard ◽  
Finn Heath ◽  
Jens Uffe Brorholt-Petersen ◽  
Henrik Kjærulf Jensen ◽  
Ole Faergeman
Keyword(s):  
Flow Cytometry ◽  
T Lymphocytes ◽  
Receptor Gene ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Receptor Expression ◽  
Low Density ◽  
Flow Cytometry Assay ◽  
Stop Mutation

Abstract We used a fluorescence flow cytometry assay with a monoclonal low density lipoprotein (LDL) receptor-specific antibody to detect LDL receptor expression on blood T lymphocytes and monocytes. We prepared peripheral blood mononuclear cells from patients with genetically verified LDL receptor-defective (Trp66-Gly mutation, n = 17) or receptor-negative (Trp23-stop mutation, n = 17) heterozygous familial hypercholesterolemia (FH) and from healthy individuals (n = 24). The cells were stimulated to express the maximum amount of LDL receptor by preincubation in lipoprotein-deficient medium. A dual-labeling technique allowed flow cytometric analysis of LDL receptor expression on cells identified by fluorescently conjugated surface marker antibodies. Knowing the LDL receptor gene mutation of the FH patients allowed us to compare the diagnostic capability of this functional assay with the DNA diagnosis and to validate the assay with molecular genetics instead of clinical indices of heterozygous FH. T lymphocytes expressed more LDL receptors and gave better diagnostic results than monocytes, and cells from patients with either the Trp66-Gly or the Trp23-stop mutation had variable but significantly reduced LDL receptor expression. The data indicate that this fluorescence flow cytometry assay is unsuitable for diagnosis of individual cases of heterozygous FH but that it may be useful for functionally characterizing mutations in the LDL receptor gene.

scholarly journals Activation of LDL Receptor Expression by Small RNAs Complementary to a Noncoding Transcript that Overlaps the LDLR Promoter

2010 ◽  
Vol 17 (12) ◽  
pp. 1344-1355 ◽  
Author(s):  
Masayuki Matsui ◽  
Fuminori Sakurai ◽  
Sayda Elbashir ◽  
Donald J. Foster ◽  
Muthiah Manoharan ◽  
...  
Keyword(s):  
Small Rnas ◽  
Ldl Receptor ◽  
Receptor Expression ◽  
Noncoding Transcript

scholarly journals Prostacyclin as a potent effector of adipose-cell differentiation

1989 ◽  
Vol 257 (2) ◽  
pp. 399-405 ◽  
Author(s):  
R Négrel ◽  
D Gaillard ◽  
G Ailhaud
Keyword(s):  
Arachidonic Acid ◽  
Cyclic Amp ◽  
Critical Role ◽  
Terminal Differentiation ◽  
Prostaglandin F2 Alpha ◽  
Adipogenic Effect ◽  
Adipose Cells

The terminal differentiation of Ob1771 pre-adipose cells induced by arachidonic acid in serum-free hormone-supplemented medium containing insulin, transferrin, growth hormone, tri-iodothyronine and fetuin (5F medium) was strongly diminished in the presence of inhibitors of prostaglandin synthesis, namely aspirin or indomethacin. Carbaprostacyclin, a stable analogue of prostacyclin (prostaglandin I2) known to be synthesized by pre-adipocytes and adipocytes, behaved as an efficient activator of cyclic AMP production and was able, when added to 5F medium, to mimic the adipogenic effect of arachidonic acid. Prostaglandins E2, F2 alpha and D2, unable to affect the cyclic AMP production, failed to substitute for carbaprostacyclin. However, prostaglandin F2 alpha, which is another metabolite of arachidonic acid in pre-adipose and adipose cells, able to promote inositol phospholipid breakdown and protein kinase C activation, potentiated the adipogenic effect of carbaprostacyclin. In addition, carbaprostacyclin enhanced both a limited proliferation and terminal differentiation of adipose precursor cells isolated from rodent and human adipose tissues maintained in primary culture. These results demonstrate the critical role of prostacyclin and prostaglandin F2 alpha on adipose conversion in vitro and suggest a paracrine/autocrine role of both prostanoids in the development of adipose tissue in vivo.

Upregulation of the Low Density Lipoprotein Receptor at the Blood-Brain Barrier: Intercommunications between Brain Capillary Endothelial Cells and Astrocytes

1987 ◽  
Vol 84 (1) ◽  
pp. 465-473
Author(s):  
Bénédicte Dehouck ◽  
Marie-Pierre Dehouck ◽  
Jean-Charles Fruchart ◽  
Roméo Cecchelli
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Blood Brain Barrier ◽  
Ldl Receptor ◽  
Receptor Expression ◽  
Brain Barrier ◽  
Brain Capillary ◽  
Ldl Receptors ◽  
Brain Capillary Endothelial Cells ◽  
Capillary Endothelial Cells

In contrast to the endothelial cells in large vessels where LDL receptors are downregulated, brain capillary endothelial cells in vivo express an LDL receptor. Using a cell culture model of the blood-brain barrier consisting of a coculture of brain capillary endothelial cells and astrocytes, we observed that the capacity of endothelial cells to bind LDL is enhanced threefold when cocultured with astrocytes. We next investigated the ability of astrocytes to modulate endothelial cell LDL receptor expression. We have shown that the lipid requirement of astrocytes increases the expression of endothelial cell LDL receptors. Experiments with dialysis membranes of different pore size showed that this effect is mediated by a soluble factor(s) with relative molecular mass somewhere between 3,500 and 14,000. Substituting astrocytes with smooth muscle cells or brain endothelium with endothelium from the aorta or the adrenal cortex did not enhance the luminal LDL receptor expression on endothelial cells, demonstrating the specificity of the interactions. This factor(s) is exclusively secreted by astrocytes cocultured with brain capillary endothelial cells, but it also upregulates the LDL receptor on other cell types. This study confirms the notion that the final fine tuning of cell differentiation is under local control.

Sign in / Sign up

Export Citation Format

Share Document