Metabolism of homologous and heterologous lipoproteins by cultured rat and human skin fibroblasts

Drevon, Christian A.; Attie, Alan D.; Pangburn, Sharon; Steinberg, Daniel

doi:10.1016/s0022-2275(20)34738-6

Cited by 103 publications

(7 citation statements)

References 32 publications

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“…On examination by PAGE in the presence of SDS, the human LDL fraction contained only apoprotein B, whereas rat LDL fraction was actually represented by 85-90% apoprotein B and 10-15% apoprotein E (as estimated by densitometric scanning). A similar pattern was earlier reported in the literature (15,48,74).…”

Section: Characterization Of Ldlsupporting

confidence: 92%

“…(a) Rat low-density lipoprotein (LDL) (density [d] = 1.02-1.045 g/ml) was separated from pooled rat serum by differential ultracentrifagation (15,26,48).…”

Section: Isolation Of Lipoproteinsmentioning

confidence: 99%

“…As expected, as compared to rat LDL, human LDL bound less extensively to rat LDL receptors. However, because of the known homogeneity of the human LDL fraction (15,26,48), the quantitative work was done with human LDL. The emerged figures, though considered underestimates, have been used as relative values which may reflect the nature and some particulars of the process, and not its absolute magnitude.…”

Section: Generalmentioning

confidence: 99%

“…The major goal of this inquiry was to identify the nature of LDL transport across the endothelium in situ. In addition to using rat LDL, we also used human LDL, though the intensity of its binding to rat LDL receptors was expected to be much lower than that of rat LDL, as indicated by the published data on fibroblasts and smooth muscle cells (12,15,32,66).…”

mentioning

confidence: 99%

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Visualization of the binding, endocytosis, and transcytosis of low-density lipoprotein in the arterial endothelium in situ.

Vasile¹,

Simionescu²,

Simiónescu³

1983

The Journal of Cell Biology

326

152

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We investigated the interaction and transport of low-density lipoprotein (LDL) through the arterial endothelium in rat aorta and coronary artery, by perfusing in situ native, untagged human, and rat LDL. The latter was rendered electron-opaque after it interacted with the endothelial cell and was subsequently fixed within tissue. We achieved LDL electronopacity by an improved fixation procedure using 3,3'-diaminobenzidine, and mordanting with tannic acid. The unequivocal identification of LDL was implemented by reacting immunocytochemically the perfused LDL with anti LDL-horseradish peroxidase conjugate. Results indicate that LDL is taken up and internalized through two parallel compartmented routes. (a) A relatively small amount of LDL is taken up by endocytosis via: (i) a receptor-mediated process (adsorptive endocytosis) that involved coated pits/vesicles, and endosomes, and, probably, (ii) a receptor-independent process (fluid endocytosis) carried out by a fraction of plasmalemmal vesicles. Both mechanisms bringing LDL to lysosomes supply cholesterol to the endothelial cell itself. (b) Most circulating LDL is transported across the endothelial cell by transcytosis via plasmalemmal vesicles which deliver LDL to the other cells of the vessel wall. Endocytosis is not enhanced by increasing LDL concentration, but the receptor-mediated internalization decreases at low temperature. Transcytosis is less modified by low temperature but is remarkably augmented at high concentration of LDL. While the endocytosis of homologous (rat) LDL is markedly more pronounced than that of heterologous (human) LDL, both types of LDL are similarly transported by transcytosis. These results indicate that the arterial endothelium possesses a dual mechanism for handling circulating LDL: by a high affinity process, endocytosis secures the endothelial cells' need for cholesterol; by a low-affinity nonsaturable uptake process, transcytosis supplies cholesterol to the other cells of the vascular wall, and can monitor an excessive accumulation of plasma LDL. Since in most of our experiments we used LDL concentrations above those found in normal rats, we presume that at low LDL concentrations saturable high-affinity uptake would be enhanced in relation to nonsaturable pathways.

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Section: Characterization Of Ldlsupporting

confidence: 92%

“…(a) Rat low-density lipoprotein (LDL) (density [d] = 1.02-1.045 g/ml) was separated from pooled rat serum by differential ultracentrifagation (15,26,48).…”

Section: Isolation Of Lipoproteinsmentioning

confidence: 99%

Section: Generalmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Visualization of the binding, endocytosis, and transcytosis of low-density lipoprotein in the arterial endothelium in situ.

Vasile¹,

Simionescu²,

Simiónescu³

1983

The Journal of Cell Biology

326

152

View full text Add to dashboard Cite

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“…8). Both enzymes are controlled by the cellular concentration of sterols (40)(41)(42). ACAT functions as a cholesterol buffer in the cells; an elevated pool of intracellular cholesterol will cause increased esterification of cholesterol (43).…”

Section: Discussionmentioning

confidence: 99%

Effect of a coffee lipid (cafestol) on cholesterol metabolism in human skin fibroblasts

Halvorsen

Ranheim

Nenseter

et al. 1998

Journal of Lipid Research

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Consumption of boiled coffee promotes an elevation of plasma cholesterol concentration in humans. The active compounds found in the lipid fraction of the coffee have been identified as the diterpenes cafestol and kahweol. We have studied the effects of pure cafestol on cholesterol metabolism in human skin fibroblasts (HSF). The uptake of [ 125 I]labeled tyramine cellobiose-labeled low density lipoprotein ([ 125 I]TC-LDL) was decreased by about 50% ( P Ͻ 0.05) after 18 h preincubation time with cafestol (20 g/ml), as compared to the control cells. The specific binding of radiolabeled LDL was reduced by 54% ( P Ͻ 0.05) after preincubation for 18 h with cafestol. A reduced amount of LDL receptors was demonstrated by a protein-normalized Scatchard plot analysis (20% decrease in B max ) as well as by immunoblotting (25%) after cafestol incubation. No significant effect was observed on the level of mRNA for the LDL receptor after 11 and 23 h incubation with cafestol. Furthermore, we transfected HSF cells with a promoter region for the LDL receptor gene linked to a reporter gene, chloramphenicol acetyl transferase (CAT). No change was seen in the CAT activity after incubation with cafestol (20 g/ml). Moreover, cafestol caused a 2.3-fold ( P Ͻ 0.05) higher incorporation of radiolabeled [ 14 C]oleic acid into cholesteryl esters after 24 h incubation, as compared to control cells, suggesting an increased acyl-CoA:cholesterol acyl transferase (ACAT) activity. Incorporation of [ 14 C]acetate into cholesterol was reduced by approximately 40% ( P Ͻ 0.05) with cafestol (20 g/ml), as compared to control after 24 h preincubation, indicating a decreased 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase activity. Our results suggest that intake of cafestol may cause increased concentration of plasma cholesterol via the down-regulation of low density lipoprotein receptors by post-transcriptional mechanisms. -Halvorsen, B., T. Ranheim, M. S. Nenseter, A. C. Huggett, and C. A. Drevon. Effect of a coffee lipid (cafestol) on cholesterol metabolism in human skin fibroblasts.

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Hepatic Catabolism of Low Density Lipoprotein: Mechanisms and Metabolic Consequences

2007

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The purpose of this short review is to summarize information currently available about the extent to which the liver takes up and degrades low-density lipoprotein (LDL), the mechanism of uptake, and its metabolic consequences. One reason for a review on this narrowly defined topic is recent evidence establishing that the liver in most animals probably accounts for more than 50% of total body LDL degradation, as will be discussed in detail. The corollary of that finding is that regulation of hepatic degradation may, therefore, be crucial in determining steady-state plasma levels of LDL. Indeed, it is already clear that some drugs act to lower LDL levels by regulating hepatic LDL receptor number. A second reason for choosing to review hepatic LDL catabolism is that studies of cultured hepatocytes are beginning to shed light on alternative, low-affinity pathways for LDL uptake; these pathways may have different metabolic consequences than uptake via specific, receptor-mediated pathways. Before discussing LDL catabolism, however, it may be useful to place it in context by briefly reviewing the overall participation of the liver in lipoprotein metabolism. HEPATIC LIPOPROTEIN METABOLISM:A CAPSULE VIEW The liver is the major source of plasma lipoproteins, secreting mainly very low-density lipoproteins (VLDL) and high-density lipoproteins (HDL). The intestine can also synthesize and secrete these lipoproteins in addition to its major contribution, the chylomicrons. But the intestinal contribution to VLDL and HDL production is probably much less than that of the liver.

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Metabolism of homologous and heterologous lipoproteins by cultured rat and human skin fibroblasts

Cited by 103 publications

References 32 publications

Visualization of the binding, endocytosis, and transcytosis of low-density lipoprotein in the arterial endothelium in situ.

Visualization of the binding, endocytosis, and transcytosis of low-density lipoprotein in the arterial endothelium in situ.

Effect of a coffee lipid (cafestol) on cholesterol metabolism in human skin fibroblasts

Hepatic Catabolism of Low Density Lipoprotein: Mechanisms and Metabolic Consequences

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