Transfer of cholesterol from its site of synthesis to the plasma membrane.

Lange, Yvonne; Matthies, H

doi:10.1016/s0021-9258(17)42647-0

Cited by 115 publications

(9 citation statements)

References 24 publications

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“…This may reflect impaired movement of LDL-derived cholesterol from lysosomes to cell membranes. Although recent progress has been made in elucidating the kinetics and mechanism of movement of newly synthesized cholesterol from the endoplasmic reticulum to the plasma membrane (17,19,20), the mechanism and pathway of intracellular transport of LDL-cholesterol remains unknown.…”

Section: Discussionmentioning

confidence: 99%

“…These transport experiments provide only relative rates of intracellular cholesterol movement for the two fibroblast lines. It is not possible to derive information on the absolute kinetics of intracellular [3H]cholesterol movement using this protocol, because the cholesterol exhange rate between cellular membranes and lipid vesicles is slow compared to the reported transport rates of endogenously derived cholesterol (11,19). No experiments have reported the intracellular movement of exogenously derived cholesterol.…”

Section: Movement Of Ldl-derived and Endogenously Synthesized Cholesterol To The Plasma Membrane In Normal And Npc Cellsmentioning

confidence: 99%

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The intracellular transport of low density lipoprotein-derived cholesterol is defective in Niemann-Pick type C fibroblasts.

Liscum

Ruggiero

Faust

1989

The Journal of Cell Biology

285

200

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Abstract. Niemann-Pick disease type C (NPC) is characterized by substantial intracellular accumulation of unesterified cholesterol. The accumulation of unesterified cholesterol in NPC fibroblasts cultured with low density lipoprotein (LDL) appears to result from the inability of LDL to stimulate cholesterol esterification in addition to impaired LDL-mediated downregulation of LDL receptor activity and cellular cholesterol synthesis. Although a defect in cholesterol transport in NPC cells has been inferred from previous studies, no experiments have been reported that measure the intracellular movement of LDLcholesterol specifically. We have used four approaches to assess intracellular cholesterol transport in normal and NPC cells and have determined the following: (a) mevinolin-inhibited NPC cells are defective in using (LDL) l (8). LDL is delivered to lysosomes where the protein/phospholipid coat is degraded, and LDL-cholesteryl esters are hydrolyzed to unesterified cholesterol. LDL-derived cholesterol is used by cells to synthesize cellular membranes, bile acids, and steroid hormones (8). LDL-derived cholesterol also elicits several regulatory responses, including suppression of cholesterol biosynthesis and LDL receptor activity, as well as activation of the cholesterol-esterifying enzyme, acyl coenzyme A/cholesterol acyl transferase (ACAT) (8). The process of receptor-mediated internalization of LDL and the effects of LDL-cholesterol on cellular cholesterol metabolism have been extensively studied (8); however, little information is known about the fate of cholesterol formed by lysosomal hydrolysis of LDL-cholesteryl esters. In particular, the pathway and mechanism of intracellular transport of LDL-cholesterol from lysosomes to cellular membranes are obscure. In addition, it is not known whether the regulatory actions of LDL-cholesterol require either the transport of cholesterol to regulatory sites within cells or metabolic transformation of the sterol.Somatic cells exhibiting specific defects in LDL metabolism may be useful in delineating the mechanisms of intracellular transport of and regulation by LDL-cholesterol. A defect in LDL-cholesterol metabolism in fibroblasts from patients with Niemann-Pick disease type C (NPC) has been described by Pentchev and co-workers (25-27) and our laboratory (21). Although LDL is bound and internalized, and the cholesteryl esters hydrolyzed normally in NPC fibroblasts, LDL-derived cholesterol does not elicit normal regulatory responses (21,(25)(26)(27). In NPC cells, LDL does not stimulate cholesterol esterification, and LDL suppression of cholesterol synthesis and LDL receptor activity is impaired (21,25,27). The defective regulation of cellular cholesterol metabolism in NPC cells appears to be specific for LDL-derived cholesterol, since 25-hydroxycholesterol, a nonlipoprotein effector, does stimulate cholesterol esterification as well as downregulate cholesterol synthesis and LDL receptor activity normally in NPC cells (21). Also, exogenously added mevalonate suppresses...

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Section: Discussionmentioning

confidence: 99%

Section: Movement Of Ldl-derived and Endogenously Synthesized Cholesterol To The Plasma Membrane In Normal And Npc Cellsmentioning

confidence: 99%

The intracellular transport of low density lipoprotein-derived cholesterol is defective in Niemann-Pick type C fibroblasts.

Liscum

Ruggiero

Faust

1989

The Journal of Cell Biology

285

200

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“…Cholesterol is synthesized on intracellular membranes where membrane cholesterol is low and transported to the plasma membrane where cholesterol content is high. This transfer is a unidirectional process (Lange & Matthies, 1984). How and why this occurs have not yet been understood.…”

Section: Discussionmentioning

confidence: 99%

Quantitative contributions of cholesterol and the individual classes of phospholipids and their degree of fatty acyl (un)saturation to membrane fluidity measured by fluorescence polarization

Wj¹,

Bw²,

Hilkmann³

1987

Biochemistry

199

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“…Knowledge of the parameters governing the spontaneous transfer of cholesterol between bilayers is necessary in order to understand the role played by spontaneous exchange of cholesterol between membranes and lipoproteins in the distribution of cholesterol in biological systems (Lange & Matthies, 1984;DeGrella & Simoni, 1982).…”

mentioning

confidence: 99%

Fraction of cholesterol undergoing spontaneous exchange between small unilamellar phosphatidylcholine vesicles

Bar¹,

Barenholz²,

Thompson³

1986

Biochemistry

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The kinetics of the spontaneous exchange of [3H]cholesterol between small unilamellar vesicles of phosphatidylcholine has been reexamined. Although first-order exchange kinetics were observed (k = 0.0117 min-1), in good agreement with previous studies, about 20% of the total cholesterol was found to be nonexchangeable in the 8-h time frame of the experiments. The size of this nonexchangeable pool was found to depend on the type of phospholipid and the temperature. It seems probable that the two pools of cholesterol defined in these experiments reflect the complex phase structure of the cholesterol-phosphatidylcholine vesicles.

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Transfer of cholesterol from its site of synthesis to the plasma membrane.

Cited by 115 publications

References 24 publications

The intracellular transport of low density lipoprotein-derived cholesterol is defective in Niemann-Pick type C fibroblasts.

The intracellular transport of low density lipoprotein-derived cholesterol is defective in Niemann-Pick type C fibroblasts.

Quantitative contributions of cholesterol and the individual classes of phospholipids and their degree of fatty acyl (un)saturation to membrane fluidity measured by fluorescence polarization

Fraction of cholesterol undergoing spontaneous exchange between small unilamellar phosphatidylcholine vesicles

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