Interaction between High Density and Low Density Lipoproteins during Uptake and Degradation by Cultured Human Fibroblasts

Miller, N. E.; Weinstein, David; Carew, Thomas E.; Koschinsky, Theodor; Steinberg, Daniel

doi:10.1172/jci108772

Cited by 107 publications

(20 citation statements)

References 41 publications

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“…Recent studies have demonstrated that HDL can bind to high-affinity sites on cells from a variety of different tissues, including rat adrenal gland (2, 3), rat testes (4), rat and canine liver (23)(24)(25)(26), bovine endothelium (25), and human skin fibroblasts (6,28,29). The physiological significance of this HDL binding has yet to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

Specific high-affinity binding of high density lipoproteins to cultured human skin fibroblasts and arterial smooth muscle cells.

Biesbroeck¹,

Oram²,

Albers³

et al. 1983

J. Clin. Invest.

185

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A B S T R A C T Binding of human high density lipoproteins (HDL, d = 1.063-1.21) to cultured human fibroblasts and human arterial smooth muscle cells was studied using HDL subjected to heparin-agarose affinity chromatography to remove apoprotein (apo) E and B. Saturation curves for binding of apo E-free 1251_ HDL showed at least two components: low-affinity nonsaturable binding and high-affinity binding that saturated at -20 1Ag HDL protein/ml. Scatchard analysis of high-affinity binding of apo E-free 125I-HDL to normal fibroblasts yielded plots that were significantly linear, indicative of a single class of binding sites. Saturation curves for binding of both '251-HDL3 (d = 1.125-1.21) and apo E-free 1251-HDL to low density lipoprotein (LDL) receptor-negative fibroblasts also showed high-affinity binding that yielded linear Scatchard plots. On a total protein basis, HDL2 (d = 1.063-1.10), HDL3 and very high density lipoproteins (VHDL, d = 1.21-1.25) competed as effectively as apo E-free HDL for binding of apo E-free 1251-HDL to normal fibroblasts. Also, HDL2, HDL3, and VHDL competed similarly for binding of 1251_ HDL3 to LDL receptor-negative fibroblasts. In contrast, LDL was a weak competitor for HDL binding. These results indicate that both human fibroblasts and arterial smooth muscle cells possess specific high affinity HDL binding sites. As indicated by enhanced LDL binding and degradation and increased sterol synthesis, apo E-free HDL3 promoted cholesterol efflux from fibroblasts. These effects also saturated at HDL3 concentrations of 20 ,g/ml, suggesting that promotion of cholesterol efflux by HDL is mediated by binding to the high-affinity cell surface sites.

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Section: Discussionmentioning

confidence: 99%

Specific high-affinity binding of high density lipoproteins to cultured human skin fibroblasts and arterial smooth muscle cells.

Biesbroeck¹,

Oram²,

Albers³

et al. 1983

J. Clin. Invest.

185

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“…Preparation of the postmitochondrial supernatant fraction and assay of HMG CoA reductase activity were performed as described by Brown et al (33) (36).…”

Section: Methodsmentioning

confidence: 99%

Individual Variation in the Effects of Dietary Cholesterol on Plasma Lipoproteins and Cellular Cholesterol Homeostasis in Man

Mistry¹,

Miller²,

Laker³

et al. 1981

J. Clin. Invest.

Self Cite

238

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A B S T R A C T The effects of dietary cholesterol on plasma lipoproteins and cholesterol homeostasis in blood mononuclear cells have been examined in healthy adults. Addition of 1,500 mg of cholesterol to the daily diet of 37 subjects for 14 d was associated with a wide range of response of plasma total cholesterol concentration (from -6 to +75 mg/dl; mean change, +29 mg!dl; P <0.001). Increases reduction of LDL receptor activity (-74%; P < 0.01), quantified as the rate of degradation of 125I-LDL to noniodide trichloroacetic acid-soluble material. These results provide the first direct evidence for the modulation of LDL receptor activity and HMG CoA reductase activity in a peripheral cell type in response to a dietary perturbation of human lipoprotein metabolism.The percentage increase in LDL cholesterol was negatively correlated with the percentage decrease in HMG CoA reductase activity (r = -0.49, P < 0.01). An additional negative correlation existed between the increment in plasma cholesterol concentration and the capacity of cells to degrade 125I-LDL after derepression by preincubation for 72 h in lipoproteindeficient medium (r = -0.74, P < 0.001). Thus, differences between individuals in the responses of the plasma lipoproteins to dietary cholesterol appear to be related in part to differences in the capacity of peripheral cells to catabolize LDL and to downregulate cholesterol synthesis.

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“…4). Intravenous injection of sterile saline into heavily infected mice (5 X 108 trypanosomes per ml of blood at 0 time) had no effect on the rising parasitemia: by 15 hr after injection, trypanosomes were too numerous to count accurately and by 19 Standard in vitro incubation conditions were used. HDL was prepared by two cycles of ultracentrifugal flotation and was concentrated roughly 9-fold relative to the original serum from which it was prepared.…”

Section: Methodsmentioning

confidence: 99%

Identification of the trypanocidal factor in normal human serum: high density lipoprotein.

Rifkin¹

1978

Proc. Natl. Acad. Sci. U.S.A.

171

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The differentiation of Trypanosoma brucei from T. rhodesiense, the causative agent of human sleeping sickness, depends on their relative sensitivities to the cytotoxic effects of normal human serum. The molecule responsible for the specific lysis of T. brucei has now been isolated. Serum lipoproteins were fractionated and purified by ultracentrifugal flotation and chromatography on Bio-Gel A-5m. Trypanocidal activity was recovered in te high density lipoprotein fraction (density, 1.063-1.216 g/ml). Contamination by other serum proteins was checked by crossed immunoelectrophoresis and sodium dodecyl sulfate/acrylamide gel electrophoresis. Only a trace of fl-lipoprotein was found. The trypanocidal activity of pure human high density lipoprotein was identical to that of unfractionated serum when the following were tested: (i) time course of in vitro lysis of T. brucei; (i1) in vivo destruction of T.brucei; (iif) relative resistance of T. rhodesiense to lysis. Rat or rabbit high density lipoprotein had no trypanocidal activity.

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Interaction between High Density and Low Density Lipoproteins during Uptake and Degradation by Cultured Human Fibroblasts

Cited by 107 publications

References 41 publications

Specific high-affinity binding of high density lipoproteins to cultured human skin fibroblasts and arterial smooth muscle cells.

Specific high-affinity binding of high density lipoproteins to cultured human skin fibroblasts and arterial smooth muscle cells.

Individual Variation in the Effects of Dietary Cholesterol on Plasma Lipoproteins and Cellular Cholesterol Homeostasis in Man

Identification of the trypanocidal factor in normal human serum: high density lipoprotein.

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