Membrane properties of oxysterols. Interfacial orientation, influence on membrane permeability and redistribution between membranes

Theunissen, J.J.H.; Jackson, Richard L.; Kempen, H.J.M.; Demel, R.A.

doi:10.1016/0005-2736(86)90499-2

Cited by 118 publications

(93 citation statements)

References 36 publications

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“…7␤-Hydroxycholesterol has been reported to be redistributed between a monomolecular layer and lipoproteins at a rate considerably slower than that of 25-hydroxycholesterol (8). As shown in Fig.…”

Section: Discussionmentioning

confidence: 90%

“…Increasing the area of the membrane is likely to facilitate desorption of an oxysterol from it. Based on biophysical studies, it has been suggested that there may be a perpendicular shuttling of 25-hydroxycholesterol between the inner and outer monolayer of the membrane, causing a local disordering of the lipids and a higher permeability of the membrane (8) (Fig. 4).…”

Section: Discussionmentioning

confidence: 99%

“…Using a phospholipid monolayer system Theunissen et al (8) investigated different membrane properties of the cholesterol auto-oxidation products 7-ketocholesterol, 7 ␣ -hydroxycholesterol, 7 ␤ -hydroxycholesterol, and 25-hydroxycholesterol. In this study, position dependent effects of the hydroxyl or keto group on the membrane properties (e.g., interfacial orientation, membrane surface area, and membrane condensation) of the oxysterols were observed, with a clear division between the properties of oxysterols hydroxylated in the side chain or the nucleus.…”

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confidence: 99%

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On the rate of translocation in vitro and kinetics in vivo of the major oxysterols in human circulation

Meaney

Bodin

Diczfalusy

et al. 2002

Journal of Lipid Research

152

113

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Oxysterols possess powerful biological activities. Some of their effects on the regulation of key enzymes are similar to those of cholesterol, but are much more potent. One of the critical properties of oxysterols is their ability to pass lipophilic membranes at a high rate. Transfer of unesterified 25-hydroxycholesterol from red blood cells to plasma has been reported to occur more than 1,000 times faster than cholesterol. Here we have measured the relative rate of such translocation of the three major oxysterols in human circulation: 27-hydroxycholesterol, 24S-hydroxycholesterol, and 4 ␤ -hydroxycholesterol. The distance from the 3 ␤ -hydroxyl group to the additional hydroxyl group is the greatest possible in 27-hydroxycholesterol and the least possible in 4 ␤ -hydroxycholesterol. The rate of exchange between erythrocytes and plasma was found to be high for 27-hydroxycholesterol and 24S-hydroxycholesterol, and hardly possible to measure for 4 ␤ -hydroxycholesterol and cholesterol. When injected intravenously into humans, deuterium labeled 24-and 27-hydroxycholesterol caused an immediate high enrichment of the corresponding plasma sterols followed by a decay. After injection of labeled 4 ␤ -hydroxycholesterol, the maximum deuterium enrichment occurred after 2-3 h, when secretion of the oxysterol from the liver is likely to be the limiting factor. When radiolabeled cholesterol was injected under the same conditions, maximum appearance of label occurred after about 2 days. The results illustrate the importance of the position of the additional oxygen in oxysterols and are discussed in relation to the rate of metabolism and biological effects of these oxysterols.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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On the rate of translocation in vitro and kinetics in vivo of the major oxysterols in human circulation

Meaney

Bodin

Diczfalusy

et al. 2002

Journal of Lipid Research

152

113

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“…The partition coefficient of 25-OHC between aqueous and liposomal phases, determined with liposomes containing various cholesterol: phospholipid ratios, is between 0.32 and 0.39 compared with zero for cholesterol and 25-OHC can exist as a monomer in aqueous solution at physiologically relevant concentrations (61). The relatively polar 25-OHC, as well as certain other oxysterols, has been shown to exchange rapidly between artificial liposomes and between liposomes and acceptors such as HDL 3 , but interestingly, lipid free apoA-I and apoE did not stimulate oxysterol release (36,66). On the basis of these and other studies, it has been widely assumed that the relatively rapid efflux of oxysterols such as 25-OHC and 27-OHC from various cell types to exogenous acceptors is the result of a passive exchange process and oxidation of cholesterol to products, such as 27-hydroxycholesterol has been proposed as a mechanism by which some cell types enhance cholesterol elimination (18,60).…”

Section: Discussionmentioning

confidence: 99%

ABCA1 mediates high-affinity uptake of 25-hydroxycholesterol by membrane vesicles and rapid efflux of oxysterol by intact cells

Tam¹,

Mok²,

Chimini³

et al. 2006

American Journal of Physiology-Cell Physiology

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Binding Cassette (ABC) transporter, ABCA1, plays a pivotal role in reverse cholesterol transport by mediating the cellular efflux of phospholipid and cholesterol. Studies using intact cells strongly suggest that ABCA1 acts as a phospholipid floppase, but there has been no direct demonstration that the protein is a primary active sterol transporter. Using membrane vesicles from insect Sf21 cells, we found that ABCA1 mediated ATP-dependent uptake of [ 3 H]25-hydroxycholesterol with an apparent K m of 0.7 M. Consistent with this high apparent affinity, expression of ABCA1 in human embryonic kidney cells both increased rapid efflux of 25-hydroxcholesterol and prevented oxysterol-mediated repression of low-density lipoprotein (LDL) receptor and 3-hydroxy-3-methylglutaryl-coenzyme A (HMGCoA) reductase mRNAs. Comparison of wild-type and ABCA1 Ϫ/Ϫ murine fibroblasts indicates that 25-hydroxycholesterol is effluxed ϳ5-fold more rapidly by wild-type cells. In addition, the rate of efflux from the wild-type but not the ABCA1 Ϫ/Ϫ fibroblasts is increased a further twofold by inducers of ABCA1 expression. Thus under the experimental conditions employed, endogenous ABCA1 is a major contributor to 25-hydroxycholesterol efflux from wild-type fibroblasts. Evidence from in vitro studies indicates that oxysterols are potent inducers of genes involved in cellular cholesterol efflux and metabolism, including the ABCA1 gene, and repressors of genes involved in cholesterol synthesis or uptake. Our observations raise the possibility that efflux of oxysterols by ABCA1 could contribute to a homeostatic mechanism, which both attenuates oxysterol-induced expression of its cognate gene and alleviates repression of genes encoding proteins, such as HMG-CoA reductase and LDL receptor. active transport; cholesterol homeostasis THE ATP BINDING CASSETTE (ABC) protein, ABCA1, was identified during a search for novel ABC proteins expressed in macrophages and at the time of its discovery, its function was unknown (34). Defects in the ABCA1 gene were subsequently shown to be the cause of Tangier disease, which is characterized by a lack, or abnormally low level, of high-density lipoprotein (HDL) and a markedly increased risk of coronary artery disease (5,7,11,56). Studies (2, 6, 14) using knockout mice have confirmed that ABCA1 plays a pivotal role in reverse cholesterol transport and in vitro, increased expression of the protein in several cell types results in elevated net efflux of cellular cholesterol and phospholipids. This efflux is dependent on the presence of an acceptor such as lipid-poor HDL or apolipoprotein A (apoA)-I (19, 70). Other proteins can also act as acceptors although their physiological relevance is presently unclear (46).The mechanism by which ABCA1 mediates efflux of cholesterol and phospholipids remains poorly defined. ABC transporters typically use the energy of ATP binding and hydrolysis to drive the transport of substrate across cellular membranes (26). In the case of hydrophobic compounds, transport is thought to involve ...

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“…34 Cholesterol oxides bind to specific membrane receptors or cytosolic binding proteins, leading to the perturbation of cholesterol synthesis. [35][36][37] It was also shown that 7b-hydroxycholesterol (7b-OHchol) and 7-ketocholesterol may initiate nonapoptotic death in U937 cells. 38 These findings highlight the many biological effects of cholesterol oxides.…”

Section: Introductionmentioning

confidence: 99%

Different apoptotic mechanisms are involved in the antiproliferative effects of 7β-hydroxysitosterol and 7β-hydroxycholesterol in human colon cancer cells

et al. 2004

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Plant sterols are found in fruits and vegetables. Their cholesterol-lowering effect is well documented. Our study aimed at comparing antiproliferative effects of 7b-hydroxysitosterol (7b-OHsito) versus 7b-hydroxycholesterol (7b-OHchol) on the human colon cancer cell line Caco-2. When cells were exposed for 32 h to 60 lM 7b-OHsito or to 30 lM 7b-OHchol, both compounds caused 50% growth inhibition. Cells treated with 7b-OHsito showed enhanced caspase-9 and -3 activities followed by DNA fragmentation. In contrast, 7b-OHchol did not activate caspase-3 and activation of caspase-9 and DNA fragmentation were delayed. The treatment of cells with the caspase inhibitor Z-VAD.fmk retarded the 7b-OHsito-induced apoptotic process but not that triggered by 7b-OHchol. Our data suggest that the two compounds in spite of their structural similarities target different cellular pathways, which lead to cell death.

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Membrane properties of oxysterols. Interfacial orientation, influence on membrane permeability and redistribution between membranes

Cited by 118 publications

References 36 publications

On the rate of translocation in vitro and kinetics in vivo of the major oxysterols in human circulation

On the rate of translocation in vitro and kinetics in vivo of the major oxysterols in human circulation

ABCA1 mediates high-affinity uptake of 25-hydroxycholesterol by membrane vesicles and rapid efflux of oxysterol by intact cells

Different apoptotic mechanisms are involved in the antiproliferative effects of 7β-hydroxysitosterol and 7β-hydroxycholesterol in human colon cancer cells

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