Effects of cholestyramine on receptor-mediated plasma clearance and tissue uptake of human low density lipoproteins in the rabbit.

Slater, Howard R.; Packard, C.J.; Bicker, S; Shepherd, James

doi:10.1016/s0021-9258(19)70450-5

Cited by 133 publications

(5 citation statements)

References 19 publications

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“…In patients with high LDL cholesterol, cholestyramine treatment decreases the hypercholesterolemia, presumably by reducing hepatic cholesterol levels and upregulating the expression of the LDLR. 154,155 In hypertriglyceridemic patients having abnormally high rates of VLDL production, cholestyramine increases plasma TG levels by further increasing VLDL production. 156 Bile acids are the major ligands responsible for activating the nuclear receptor farnesoid X receptor (FXR).…”

Section: Regulation Of Apob Secretion By Bile Acidsmentioning

confidence: 99%

The physiological and molecular regulation of lipoprotein assembly and secretion

2007

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Triglycerides are insoluble in water and yet are transported at milligram per millilitre concentrations in the bloodstream. This is made possible by the ability of the liver and intestine to assemble lipid-protein emulsions (i.e. lipoproteins), which transport hydrophobic molecules. The assembly of triglyceride-rich lipoproteins requires the coordination of protein and lipid synthesis, which occurs on the cytoplasmic surface of the endoplasmic reticulum (ER), and their concerted assembly and translocation into the luminal ER secretory pathway as nascent lipoprotein particles. The availability of lipid substrate for triglyceride production and the machinery for lipoprotein assembly are highly sensitive to nutritional, hormonal, and genetic modulation. Disorders in lipid metabolism or an imbalance between lipogenesis and lipoprotein assembly can lead to hyperlipidemia and/or hepatic steatosis. We selectively review recently-identified machinery, such as transcription factors and nuclear hormone receptors, which provide new clues to the regulation of lipoprotein secretion.

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Section: Regulation Of Apob Secretion By Bile Acidsmentioning

confidence: 99%

The physiological and molecular regulation of lipoprotein assembly and secretion

2007

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“…This receptor recognizes lipoproteins which contain apo B or apo E. After binding to the LDL receptor, LDL is taken into the cell by absorptive endocytosis and is degraded in lysosomes, providing cholesterol for use by the cell (Goldstein & Brown, 1977). Cholesterol supplied in this manner is used for diverse purposes, which include membrane synthesis (Brown & , production of bile acids in the liver (Slater et al, 1980) and production of steroid hormones in the adrenal cortex .…”

mentioning

confidence: 99%

A comparison of the low-density-lipoprotein receptor from bovine adrenal cortex, rabbit and rat liver and adrenal glands by lipoprotein blotting

Kroon¹,

Thompson²,

Chao³

1984

Biochemical Journal

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This paper describes the use of lipoprotein blotting to detect low-density-lipoprotein (LDL) receptors in rat and rabbit liver and adrenal glands and in bovine adrenal glands. Using this technique we show that the rabbit and rat liver LDL receptors have Mr values of 128000 and 145000 respectively. Mr values for the rabbit, rat and bovine adrenal receptors are 131000, 142000 and 132000 respectively. Differences between the bovine adrenal and rat liver receptors are not due to differences in the degree of sialylation. Lipoprotein blotting can be used to detect dietary- and drug-induced changes in the concentrations of LDL receptors. When rabbits are fed on a cholesterol-rich diet, liver LDL receptors cannot be detected, consistent with the suppression of hepatic LDL receptors by cholesterol feeding. Pharmacological doses of 17 alpha-ethinyloestradiol cause a marked increase in hepatic LDL-receptor activity in the rat. This is accompanied by a corresponding increase in the number of LDL receptors detected by lipoprotein blotting. The Mr of the induced receptor is identical with that of the receptor from control rats, which suggests that the induced receptors are produced by the same gene as LDL receptors normally present in the liver.

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“…The liver is important in the catabolism of LDL (Slater et al, 1980;Portman et al, 1979;Calvert et al, 1975;Pittman et al, 1979aPittman et al, ,b, 1980Attie et al, 1980), although the mechanisms by which LDL may interact with the liver are not entirely clear. The liver accumulates injected LDL (Slater et al, 1980;Sniderman et al, 1975;Portman et al, 1979;Calvert et al, 1975), and studies in rabbits (Slater et al, 1980) and estradiol-treated rats (Chao et al, 1979) suggest that approximately half the uptake of LDL is mediated by a mechanism similar to the LDL receptor. High-affinity uptake and degradation of LDL have been observed in suspended rat (Van Berkel et al, 1980;Ose et al, 1980a) and rabbit hepatocytes (Soltys & Portman, 1979).…”

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High-affinity uptake and degradation of ApoE-free high-density lipoprotein and low-density lipoprotein in cultured porcine hepatocytes

et al. 1982

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Isolated pig liver membranes contain a specific "lipoprotein binding site" that recognizes low-density lipoproteins (LDL) and apolipoprotein E (apoE) free high-density lipoprotein (HDL) [Bachorik, P. S., Kwiterovich, P. O., & Cooke, J. (1978) Biochemistry 17, 5287-5299]. We report here that a similar site exists in cultured porcine hepatocytes and that it mediates the uptake and degradation of apoE-free HDL. The binding of 125I-labeled HDL and 125I-labeled LDL (125I-HDL and 125I-LDL, respectively) at 4 degrees C and the uptake and degradation of the lipoproteins at 37 degrees C were time dependent and saturable and were not inhibited by unrelated proteins. Chloroquine (6 x 10(-5)M) inhibited the degradation of 125I-HDL by 76% and of 125I-LDL by greater than 99%; leupeptin inhibited the degradation of both lipoproteins by about 25%. 125I-HDL binding (4 degrees C), uptake, and degradation (37 degrees C) were inhibited by LDL, methyl-LDL, and methyl-HDL about as well as by unlabeled HDL but were unaltered in Pronase-treated cells or in cells that were cultured for 24 h in either lipoprotein-free medium containing HDL or LDL (200 micrograms/mL). In contrast, these conditions affected the uptake and degradation of 125I-LDL disproportionately. HDL and methyl-LDL inhibited 125I-LDL uptake by 50% or more but had little effect on degradation. 125I-LDL binding was reduced by 12% and degradation by 57% in Pronase-treated cells. Preincubation of the cells with LDL (200 micrograms/mL) reduced uptake by 35% and degradation by 68%. Similar preincubation with HDL (200 micrograms/mL) increased 125I-LDL degradation by 60% but did not affect 125I-LDL uptake. The findings indicated the presence in porcine hepatocytes of at least two distinct sites for lipoproteins. One site resembled the LDL receptor and mediated 125I-LDL degradation. A second, Pronase-insensitive site recognized both HDL and LDL. This site mediated almost all of the degradation of 125I-HDL but little if any degradation of 125I-LDL.

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Effects of cholestyramine on receptor-mediated plasma clearance and tissue uptake of human low density lipoproteins in the rabbit.

Cited by 133 publications

References 19 publications

The physiological and molecular regulation of lipoprotein assembly and secretion

The physiological and molecular regulation of lipoprotein assembly and secretion

A comparison of the low-density-lipoprotein receptor from bovine adrenal cortex, rabbit and rat liver and adrenal glands by lipoprotein blotting

High-affinity uptake and degradation of ApoE-free high-density lipoprotein and low-density lipoprotein in cultured porcine hepatocytes

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