Class B Scavenger Receptors CD36 and SR-BI Are Receptors for Hypochlorite-modified Low Density Lipoprotein

Marsche, Gunther; Zimmermann, R.; Horiuchi, Seikoh; Tandon, Narendra N.; Sattler, Wolfgang; Malle, Ernst

doi:10.1074/jbc.m308428200

Cited by 67 publications

(57 citation statements)

References 76 publications

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“…Even though its extent was limited, it is conceivable that the apoptotic process plays a role in determining a progressive hypocellularity during the late stages of glomerulosclerosis. The proapoptotic effect of glycated LDL, already described in endothelial cells [44], occurs in mesangial cells at a concentration (200 nmol/l) corresponding to~10% of that seen in normal human plasma, thus indicating a very high proapoptotic activity of these particles and the potential clinical relevance of the [45], the prime receptor mediating selective cholesteryl ester uptake from lipoprotein particles. In contrast, native LDL preferentially binds to the classic LDL receptor, and subsequent internalisation leads to uptake of cholesterol and cholesteryl esters.…”

Section: Discussionmentioning

confidence: 77%

Effects of different LDL particles on inflammatory molecules in human mesangial cells

et al. 2008

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Aims/hypothesis Inflammation is a mechanism of glomerular damage in chronic glomerulopathies. LDL may increase the production of inflammatory cytokines in renal tissues. However, the relative role of native, oxidised and glycated LDL in promoting this process has been only partially elucidated. Methods We tested the inflammatory and proapoptotic effects of native, oxidised and glycated LDL in human mesangial cells (HMCs) by measuring levels of IL6, CD40 and macrophage migration inhibitory factor (MIF) genes, MIF protein, release of IL6, soluble CD40, fibronectin and laminin, early and late apoptosis, and extracellular regulated kinases (ERK) 1/2 and c-Jun N-terminal kinase (JNK) activation. Results IL6 and CD40 mRNA were dose-dependently upregulated by all three species; this was closely paralleled by their increased release. MIF mRNA was potently stimulated by modified LDL, as confirmed by immunostaining. Fibronectin and laminin release was stimulated by both oxidised and glycated, but not native, LDL. All LDL species induced some increase in late, but not early, apoptosis, and similarly activated JNK2/3 phosphorylation; in contrast, ERK1/2 phosphorylation was more strongly upregulated by oxidised than either native or glycated LDL.Conclusions In HMCs, the production and release of IL6 and CD40 is stimulated by both native and modified LDL, while MIF is more strongly stimulated by oxidised LDL. Regarding the pattern of mesangial expansion, fibronectin and laminin are upregulated by oxidised and glycated LDL. Apoptosis, if modest, is induced by all species. Intracellular signalling of native and modified LDL involves JNK2/3 and, perhaps more specifically, ERK1/2. Tight control of the lipid profile may be useful in preserving kidney function in patients with metabolic alterations.

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Section: Discussionmentioning

confidence: 77%

Effects of different LDL particles on inflammatory molecules in human mesangial cells

et al. 2008

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“…Exposure of mouse peritoneal macrophages to HOCl-oxidized LDL resulted in increased intracellular concentrations of cholesterol and cholesteryl esters, with Lys residues of apoliopoprotein B-100 representing the major oxidative target [62]. Competition studies revealed that this increased uptake is due to recognition of HOClmodified LDL by the macrophage class B scavenger receptors CD36 and SR-BI [63]. Further, the MPO/HOCl system can generate a series of secondary oxidation products, such as tyrosine radicals, p-hydroxyphenylacetaldehyde and highly reactive unsaturated aldehydes-glyceraldehyde, 2-hydroxypropanal, and acrolein [59].…”

Section: Formation Of Atherogenic Ldlmentioning

confidence: 99%

The roles of myeloperoxidase in coronary artery disease and its potential implication in plaque rupture

et al. 2016

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Atherosclerosis is the main pathophysiological process underlying coronary artery disease (CAD). Acute complications of atherosclerosis, such as myocardial infarction, are caused by the rupture of vulnerable atherosclerotic plaques, which are characterized by thin, highly inflamed, and collagen-poor fibrous caps. Several lines of evidence mechanistically link the heme peroxidase myeloperoxidase (MPO), inflammation as well as acute and chronic manifestations of atherosclerosis. MPO and MPO-derived oxidants have been shown to contribute to the formation of foam cells, endothelial dysfunction and apoptosis, the activation of latent matrix metalloproteinases, and the expression of tissue factor that can promote the development of vulnerable plaque. As such, detection, quantification and imaging of MPO mass and activity have become useful in cardiac risk stratification, both for disease assessment and in the identification of patients at risk of plaque rupture. This review summarizes the current knowledge about the role of MPO in CAD with a focus on its possible roles in plaque rupture and recent advances to quantify and image MPO in plasma and atherosclerotic plaques.

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“…4C). DISCUSSION SR-BI is a multi-ligand cell surface receptor and capable of binding HDL, LDL, VLDL, modified LDL, BSA, and liposomes containing anionic phospholipids (27)(28)(29)(30). Although the function of SR-BI in the selective uptake of CE from HDL is indisputable (35), conflicting information on a potential role in VLDL and LDL turnover has been described (37,38,47).…”

Section: Effect Of Sr-bi Deficiency On the Kinetics Of Tg-rich Chylommentioning

confidence: 99%

“…Recently, it was shown that lipid-free apoE binds to SR-BI and enhances CE uptake from lipoproteins (26). In addition to HDL, SR-BI was found to bind a broad spectrum of ligands, including modified lipoproteins (acetylated LDL, oxidized LDL, and hypochlorite-modified LDL), native lipoproteins (HDL, LDL, and very low density lipoproteins (VLDL)), maleylated bovine serum albumin (BSA), and anionic phospholipids (27)(28)(29)(30). In contrast, SR-BI does not bind polyanions (e.g.…”

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confidence: 99%

Scavenger Receptor BI Plays a Role in Facilitating Chylomicron Metabolism

Out¹,

Kruijt²,

Rensen³

et al. 2004

Journal of Biological Chemistry

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The function of scavenger receptor class B type I (SR-BI) in mediating the selective uptake of high density lipoprotein (HDL) cholesterol esters is well established. However, the potential role of SR-BI in chylomicron and chylomicron remnant metabolism is largely unknown. In the present investigation, we report that the cell association of 160 nm-sized triglyceride-rich chylomicronlike emulsion particles to freshly isolated hepatocytes from SR-BI-deficient mice is greatly reduced (>70%), as compared with wild-type littermate mice. Competition experiments show that the association of emulsion particles with isolated hepatocytes is efficiently competed for (>70%) by the well established SR-BI ligands, HDL and oxidized low density lipoprotein (LDL), whereas LDL is ineffective. Upon injection into SR-BI-deficient mice the hepatic association of emulsion particles is markedly decreased (ϳ80%) as compared with wild-type mice. The relevance of these findings for in vivo chylomicron (remnant) metabolism was further evaluated by studying the effect of SR-BI deficiency on the intragastric fat load-induced postprandial triglyceride response. The postprandial triglyceride response is 2-fold higher in SR-BI-deficient mice as compared with wild-type littermates (area-under-the-curve 39.6 ؎ 1.2 versus 21.1 ؎ 3.6; p < 0.005), with a 4-fold increased accumulation of chylomicron (remnant)-associated triglycerides in plasma at 6 h after intragastric fat load. We conclude that SR-BI is important in facilitating chylomicron (remnant) metabolism and might function as an initial recognition site for chylomicron remnants whereby the subsequent internalization can be exerted by additional receptor systems like the LDL receptor and LDL receptor-related protein. Chylomicrons are triglyceride (TG)1 -rich lipoproteins that transport dietary lipids from the intestine to the liver. Upon entering the circulation, chylomicrons are converted to remnants by the TG-hydrolyzing action of lipoprotein lipase (LPL) and the acquisition of apolipoproteins (apo) such as apoE. Chylomicron remnants are subsequently taken up by the liver by an apoE-mediated process (reviewed in Refs. 1-3). The essential role of apoE in remnant clearance was indicated by the accumulation of remnants in apoE-deficient mice (4). It has been suggested that several apoE-dependent recognition sites contribute to the removal of remnants, including the low-density lipoprotein (apoB and -E) receptor (LDLr) (4 -9), and the LDLr-related protein/␣ 2 -macroglobulin receptor (LRP) (8, 10, 11). It is generally accepted, however, that for the initial liver recognition of remnants, the so-called "capture step," additional systems are needed. The initial sequestration step was suggested to involve heparan sulfate proteoglycans (5, 12), the lipolysis-stimulated receptor (13-15), a TG-rich lipoprotein receptor (16, 17), the asialoglycoprotein receptor (18), LPL (19), and/or hepatic lipase (20), while we also provided evidence for a specific remnant receptor (21-23) to function as an initial re...

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Class B Scavenger Receptors CD36 and SR-BI Are Receptors for Hypochlorite-modified Low Density Lipoprotein

Abstract: The presence of HOCl-modified epitopes inside and outside monocytes/macrophages and the presence of HOCl-modified apolipoprotein B in atherosclerotic lesions has initiated the present study to identify scavenger receptors that bind and internalize HOCl-low density lipoprotein (

Cited by 67 publications

References 76 publications

Effects of different LDL particles on inflammatory molecules in human mesangial cells

Effects of different LDL particles on inflammatory molecules in human mesangial cells

The roles of myeloperoxidase in coronary artery disease and its potential implication in plaque rupture

Scavenger Receptor BI Plays a Role in Facilitating Chylomicron Metabolism

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