α‐Helical requirements for free apolipoproteins to generate HDL and to induce cellular lipid efflux

Hara, Hitoshi; Hara, Hiroko; Komaba, Akira; Yokoyama, Shinji

doi:10.1007/bf02536480

Cited by 64 publications

(32 citation statements)

References 39 publications

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“…These results strongly suggest that le represents the mean Of duplicate dishes (3.5%/ coefficient )n). surface, as has been described previously for the interaction of sure of fibroblasts to apo A-I or 37pA increased efflux HDL apolipoproteins with cells (28,32). This property may plasma membrane of both cholesterol and phosphaticonfer specificity for lipid-poor subclasses of HDL particles ie in parallel to depletion of ACAT-accessible choleswhich have more helices exposed for cellular interactions (7, plying that these three lipid transport processes are 33,34 Previous studies showed that modifying HDL so as to decrease its interaction with cellular high-affinity binding sites also reduces its ability to remove excess cellular cholesterol (4,5,(35)(36)(37), suggesting that these two processes are closely I .…”

Section: Discussionsupporting

confidence: 53%

Synthetic amphipathic helical peptides that mimic apolipoprotein A-I in clearing cellular cholesterol.

Mendez¹,

Anantharamaiah²,

Segrest³

et al. 1994

J. Clin. Invest.

178

149

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Clearance of excess cholesterol from cells by HDL is facilitated by the interaction of HDL apolipoproteins with cellsurface binding sites or receptors, a process that may be important in preventing atherosclerosis. In this study, synthetic peptides containing 18-mer amphipathic helices of the class found in HDL apolipoproteins (class A) were tested for their abilities to remove cholesterol and phospholipid from cultured sterol-laden fibroblasts and macrophages and to interact with cell-surface HDL binding sites. Lipid-free peptides containing two identical tandem repeats of class A amphipathic helices promoted cholesterol and phospholipid efflux from cells and depleted cellular cholesterol accessible for esterification by acyl CoA/cholesterol acyltransferase, similar to what was observed for purified apolipoprotein A-I. Peptide-mediated removal of plasma membrane cholesterol and depletion of acyl CoA/cholesterol acyltransferaseaccessible cholesterol appeared to occur by separate mechanisms, as the latter process was less dependent on extracellular phospholipid. The dimeric amphipathic helical peptides also competed for high-affinity HDL binding sites on cholesterol-loaded fibroblasts and displayed saturable high-affinity binding to the cell surface. In contrast, peptides with a single helix had little or no ability to remove cellular cholesterol and phospholipid, or to interact with HDL binding sites, suggesting that cooperativity between two or more helical repeats is required for these activities. Thus, synthetic peptides comprising dimers of a structural motif common to exchangeable apolipoproteins can mimic apolipoprotein A-I in both binding to putative cell-surface receptors and clearing cholesterol from cells. (J. Clin. Invest. 1994.

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Section: Discussionsupporting

confidence: 53%

Synthetic amphipathic helical peptides that mimic apolipoprotein A-I in clearing cellular cholesterol.

Mendez¹,

Anantharamaiah²,

Segrest³

et al. 1994

J. Clin. Invest.

178

149

View full text Add to dashboard Cite

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“…HDL is generated by the ABCA1-mediated reaction with various peptides having amphiphilic a-helical segments, including helical apolipoproteins (35,45), synthetic peptides (46,47), and even those containing only D-amino acids (44,48). Thus, there is no specific requirement of amino acid sequence for the biogenesis of HDL except for amphiphilic helices as a key conformation.…”

Section: Discussionmentioning

confidence: 99%

Serum amyloid A generates high density lipoprotein with cellular lipid in an ABCA1- or ABCA7-dependent manner

Abe-Dohmae

Kato

Kumon

et al. 2006

Journal of Lipid Research

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Serum amyloid A (SAA) is an amphiphilic helical protein that is found associated with plasma HDL in various pathological conditions, such as acute or chronic inflammation. Cellular lipid release and generation of HDL by this protein were investigated, in comparison with the reactions by apolipoprotein A-I (apoA-I) and several types of cells that appear with various specific profiles of cholesterol and phospholipid release. SAA mediated cellular lipid release from these cells with the same profile as apoA-I. Upregulation of cellular ABCA1 protein by liver X receptor/retinoid X receptor agonists resulted in an increase of cellular lipid release by apoA-I and SAA. SAA reacted with the HEK293-derived clones that stably express human ABCA1 (293/2c) or ABCA7 (293/6c) to generate cholesterol-containing HDL in a similar manner to apoA-I. Dibutyryl cyclic AMP and phorbol 12-myristate 13-acetate, which differentiate apoA-Imediated cellular lipid release between 293/2c and 293/6c, also exhibited the same differential effects on the SAAmediated reactions. No evidence was found for the ABCA1/ ABCA7-independent lipid release by SAA. Characterization of physicochemical properties of the HDL revealed that SAA-generated HDL particles had higher density, larger diameter, and slower electrophoretic mobility than those generated by apoA-I. These results demonstrate that SAA generates cholesterol-containing HDL directly with cellular lipid and that the reaction is mediated by ABCA1 and

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“…The generally accepted model for efflux mediated by these two proteins is that the ligands for SR-BI-mediated efflux are mature, fully lipidated lipoproteins rich in PL (10,27). In contrast to SR-BI, the ligands for ABCA1-mediated efflux appear to be poorly lipidated, exchangeable apolipoproteins such as apoA-I, apoA-II, apoA-IV, and apoE (28)(29)(30)(31). This model of cellular cholesterol efflux is derived primarily from studies with cultured cells exposed to purified preparations of lipoproteins or apolipoproteins.…”

Section: Discussionmentioning

confidence: 99%

In vivo modulation of HDL phospholipid has opposing effects on SR-BI- and ABCA1-mediated cholesterol efflux

Yancey

Kawashiri

Moore

et al. 2004

Journal of Lipid Research

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The effects of in vivo modulation of HDL phospholipid (PL) on scavenger receptor class BI (SR-BI)-and ATP binding cassette transporter 1 (ABCA1)-mediated efflux were examined by overexpressing either endothelial lipase (EL) or phosphatidylserine phospholipase (PS-PLA 1 ) in human apolipoprotein A-I (apoA-I) transgenic mice. Overexpression of EL led to large reductions in the serum PL/apoA-I ratio ( ؊ 60%), total cholesterol (TC; ؊ 89%), and HDL cholesterol ( ؊ 91%). Relative to the serum before overexpression of EL, the efflux potential of the serum via SR-BI decreased by 90% and ABCA1-mediated efflux increased by 63%. In contrast to overexpression of EL, overexpression of PS-PLA 1 led to increases in the PL/apoA-I ratio (88%), TC (78%), HDL cholesterol (57%), and HDL size. The efflux potential of the serum increased by 60% via SR-BI and decreased by 57% via ABCA1. There were significant positive correlations between SR-BI-mediated efflux and a number of serum parameters, including PL/apoA-I ratio, PL, TC, free cholesterol (FC), and HDL cholesterol. In striking contrast, the same correlations were seen with ABCA1-mediated efflux, but the relationships were inverse. In summary, in vivo modulation of HDL PL content affects ABCA1-and SR-BI-mediated efflux in a reciprocal manner. These findings indicate that the type of lipase acting on HDL in vivo will determine which FC efflux pathway the HDL serves. Additionally, the extent of lipolysis will determine the efficiency of FC removal via this pathway. HDL cholesterol levels are inversely correlated with the incidence of coronary artery disease (1-4). One mechanism by which HDL is thought to protect against atherosclerosis is by the removal of excess free cholesterol (FC) from peripheral cells and subsequent delivery to the liver for excretion (5-7). There are three known mechanisms by which HDL and/or its apolipoproteins can remove FC from cells. Aqueous diffusion is a relatively inefficient efflux mechanism that occurs with all cell types (8). In recent years, two proteins have been discovered that mediate efficient cholesterol efflux. The scavenger receptor class BI (SR-BI) facilitates the bidirectional flux of FC between cells and HDL (9, 10), and the ATP binding cassette transporter 1 (ABCA1) (11-13) mediates the unidirectional efflux of cellular FC and phospholipid (PL) to lipid-poor apolipoprotein A-I (apoA-I) and other exchangeable apolipoproteins. A number of studies suggest that both mechanisms of efflux may operate in atherosclerotic lesions (14-16).The goal of the present study was to determine the effects of in vivo modulation of HDL PL on both ABCA1-and SR-BI-mediated FC efflux. The importance of studying the role of HDL PL in the flux of FC between cells and HDL is supported by a number of previous observations. The efflux of cholesterol from cells to serum is correlated with HDL PL content (17, 18). Importantly, it has been demonstrated that patients with coronary artery disease have low HDL PL levels (19). Past studies have used in vitro mani...

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α‐Helical requirements for free apolipoproteins to generate HDL and to induce cellular lipid efflux

Cited by 64 publications

References 39 publications

Synthetic amphipathic helical peptides that mimic apolipoprotein A-I in clearing cellular cholesterol.

Synthetic amphipathic helical peptides that mimic apolipoprotein A-I in clearing cellular cholesterol.

Serum amyloid A generates high density lipoprotein with cellular lipid in an ABCA1- or ABCA7-dependent manner

In vivo modulation of HDL phospholipid has opposing effects on SR-BI- and ABCA1-mediated cholesterol efflux

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