Receptor-like function of heparin in the binding and uptake of neutral lipids.

Bosner, Matthew S.; Gulick, Tod; Riley, D. J. S.; Spilburg, Curtis A.; Lange, Louis G.

doi:10.1073/pnas.85.20.7438

Cited by 65 publications

(50 citation statements)

References 12 publications

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“…Charge density seems to be an important factor in the interaction (39). Because adhesion substances are secreted from the mouse (25), the head of the worms would attach to the apical surfaces of intestinal cells, where heparan sulfate proteoglycans or heparin-like molecules are expressed (41,42). However, at the time of worm expulsion, mast cell glycosaminoglycans would bind to adhesion substances of the worms and inhibit binding of the worms to intestinal epithelial cells.…”

Section: Discussionmentioning

confidence: 99%

A Role of Mast Cell Glycosaminoglycans for the Immunological Expulsion of Intestinal Nematode, Strongyloides venezuelensis

Maruyama

Yabu

Yoshida

et al. 2000

The Journal of Immunology

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We examined effects of mast cell glycosaminoglycans on the establishment of the intestinal nematode, Strongyloides venezuelensis, in the mouse small intestine. When intestinal mastocytosis occurred, surgically implanted adult worms could not invade and establish in the intestinal mucosa. In mast cell-deficient W/Wv mice, inhibition of adult worm invasion was not evident as compared with littermate +/+ control mice. Mucosal mastocytosis and inhibition of S. venezuelensis adult worm mucosal invasion was tightly correlated. To determine effector molecules for the invasion inhibition, adult worms were implanted with various sulfated carbohydrates including mast cell glycosaminoglycans. Among sulfated carbohydrates tested, chondroitin sulfate (ChS)-A, ChS-E, heparin, and dextran sulfate inhibited invasion of adult worms into intestinal mucosa in vivo. No significant inhibition was observed with ChS-C, desulfated chondroitin, and dextran. ChS-E, heparin, and dextran sulfate inhibited adhesion of S. venezuelensis adult worms to plastic surfaces in vitro. Furthermore, binding of intestinal epithelial cells to adhesion substances of S. venezuelensis, which have been implicated in mucosal invasion, was inhibited by ChS-E, heparin, and dextran sulfate. Because adult worms of S. venezuelensis were actively moving in the intestinal mucosa, probably exiting and reentering during infection, the possible expulsion mechanism for S. venezuelensis is inhibition by mast cell glycosaminoglycans of attachment and subsequent invasion of adult worms into intestinal epithelium.

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Section: Discussionmentioning

confidence: 99%

A Role of Mast Cell Glycosaminoglycans for the Immunological Expulsion of Intestinal Nematode, Strongyloides venezuelensis

Maruyama

Yabu

Yoshida

et al. 2000

The Journal of Immunology

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“…It has been shown that BSDL binds to heparin-like molecules lining the intestinal wall and that this binding is reversed by the addition of soluble heparin (10). Furthermore, BSDL located on the epithelial cell surface may facilitate the uptake of hydrolyzed dietary lipids and cholesterol (11).…”

mentioning

confidence: 99%

Site-directed Mutagenesis of the Basic N-terminal Cluster of Pancreatic Bile Salt-dependent Lipase

Aubert¹,

Sbarra

Petit-Thévenin

et al. 2002

Journal of Biological Chemistry

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Previous studies have postulated the presence of a heparin-binding site on the bile salt-dependent lipase (BSDL), whereas two bile salt-binding sites regulate the enzyme activity. One of these sites may overlap with the tentative heparin-binding site at the level of an N-terminal basic cluster consisting of positive residues Lys 32 , Lys 56 , Lys 61 , Lys 62 , and Arg 63 . The present study uses specific site-directed mutagenesis to determine the functional significance of this basic cluster. Mutations in this sequence resulted in recombinant enzymes that were able to bind to immobilized and to cell-associated heparin before moving throughout intestinal cells. Recombinant BSDL was fully active on soluble substrate, but mutants were less active on micellar cholesteryl oleate in comparison with the wild-type enzyme. Activation studies by primary (sodium taurocholate) and by secondary (sodium taurodeoxycholate) bile salts revealed that the activation of BSDL by sodium taurocholate at concentrations below the critical micellar concentration, and not that evoked by micellar bile salts, was affected by substitutions, suggesting that this Nterminal basic cluster likely represents the specific bile salt-binding site of BSDL. Substitutions also affected the activation of the enzyme promoted by anionic phospholipids, extending the function of this site to that of a cationic regulatory site susceptible to accommodate anionic ligands.

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“…It has been hypothesized that the heparin-binding site present on BSDL (Fält et al, 2001) could be involved in such binding (Bosner et al, 1988). As shown here, heparin at concentration up to 1 mg/ml only partially impaired the uptake of BSDL by the cells (as assessed by the amount of enzyme activity recorded in the basal reservoir of Transwell inserts).…”

Section: Lox-1 Implication In Bsdl Transcytosismentioning

confidence: 53%

“…Clearly, if fucose residues of BSDL are involved in the interaction of the enzyme with the LOX-1 receptor, they should not be ␣(1-2) linked to galactose residues as UEA-1 lectin did not impair BSDL transcytosis. A way to conciliate the binding of BSDL to heparin-like molecules lining the brush border membrane (see Fält et al, 2001;Bosner et al, 1988) and the implication of LOX-1 would be that BSDL first bind to heparin-like molecules lining intestinal cells and then are transferred to LOX-1 with which the enzyme associates by mean of glycannic determinants. Once bound to LOX-1, BSDL could form clusters that are taken up via clathrin-coated pits of intestinal cells (Bruneau et al, 2001).…”

Section: Lox-1 Implication In Bsdl Transcytosismentioning

confidence: 99%

“…Structural elements of BSDL potentially implicated in its interaction with a receptor present at the apical membrane of enterocytes are multiple. These are as follows: 1) the heparin-binding site present on BSDL, which could recognize heparin-like molecules lining microvilli membranes (Bosner et al, 1988); 2) N-linked glycan structures that can bind to mannose/fucose lectin receptors (Sallusto et al, 1995); and 3) finally, O-linked mucin-type structures of the C-terminal domain of BSDL (Wang et al, 1995) susceptible to bind lectin-like receptor or ligands such as selectins. It is therefore conceivable that receptor(s) present at the apical surface of intestinal cells could be involved in BSDL uptake by enterocytes (Bruneau et al, 2001(Bruneau et al, , 2003.…”

Section: Introductionmentioning

confidence: 99%

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Lectin-like Ox-LDL Receptor Is Expressed in Human INT-407 Intestinal Cells: Involvement in the Transcytosis of Pancreatic Bile Salt–dependent Lipase

Bruneau

Richard

Silvy

et al. 2003

MBoC

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We have recently shown that the pancreatic bile salt-dependent lipase (BSDL) can be taken up by intestinal cells and transported to the blood circulation. This mechanism likely involves (specific) receptor(s) able to bind BSDL and located at the apical intestinal cell membrane. In this study, using Int407 human intestinal cells cultured to form a tight epithelium, we attempted to characterize (the) BSDL receptor(s). We found that an apical 50-kDa protein was able to bind BSDL. Further, we have demonstrated that Int407 cells expressed the lectin-like oxidized-LDL receptor (LOX-1), the upregulation of which by oxidized-LDL potentiates the transcytosis of BSDL, whereas carrageenan and to a lesser extent polyinosinic acid and fucoidan decrease the enzyme transcytosis. The mAb JTX92, which blocks the LOX-1 receptor function, also impaired the BSDL transcytosis. To confirm these results, the cDNA encoding the human intestinal receptor LOX-1 has been cloned, inserted into vectors, and transfected into Int407 cells. Overexpression of LOX-1 by these cells leads to a substantial increase in the BSDL transcytosis. Globally, these data support the view that LOX-1 could be an intestinal receptor for BSDL, which is implicated in the transcytosis of this enzyme throughout Int407 cells. INTRODUCTIONThe bile salt-dependent lipase (BSDL, EC 3.1.1.13), also referred to as carboxyl ester lipase or bile salt-stimulated lipase, is a lipolytic enzyme, synthesized and secreted by the exocrine pancreas (Lombardo, 2001). The secretion of this digestive enzyme requires the participation of the Grp94 molecular chaperone (Bruneau and Lombardo, 1995;Bruneau et al., 1998). Once in the lumen of the duodenum, BSDL, in concert with other pancreatic lipolytic enzymes and preduodenal lipase, acts to complete the digestion of dietary lipids. Indeed, upon activation by primary bile salts, BSDL catalyzes the duodenal hydrolysis of cholesterol esters into free cholesterol and fatty acids before their absorption by intestinal cells (Howles et al., 1996;Weng et al., 1999). Although controversial (Howles et al., 1996), BSDL could also participate in the intestinal free cholesterol absorption (LopezCandales et al., 1993), acting as a cholesterol transfer protein (Myers-Payne et al., 1995), or as a cholesterol reesterifying enzyme after cholesterol absorption by intestinal cells (Bhat and Brockman, 1982).A fraction of BSDL, possibly associated with Grp94, reaches the vicinity of microvilli and upon binding to the surface of intestinal cells is internalized and transported up to the blood compartment (Bruneau et al., , 2000a(Bruneau et al., , 2000b(Bruneau et al., , 2003. Consequently, BSDL has been reported in the plasma of normolipidemic patients where it associates with apolipoprotein B-containing lipoproteins such as low-density lipoprotein (LDL), chylomicron and very-low-density lipoprotein (VLDL; Bruneau et al., 2003).The pathway of BSDL throughout intestinal cells has been recently delineated using Int407 cells (Bruneau et al., 2001), which do not e...

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Receptor-like function of heparin in the binding and uptake of neutral lipids.

Abstract: ABSTRACT

Cited by 65 publications

References 12 publications

A Role of Mast Cell Glycosaminoglycans for the Immunological Expulsion of Intestinal Nematode, Strongyloides venezuelensis

A Role of Mast Cell Glycosaminoglycans for the Immunological Expulsion of Intestinal Nematode, Strongyloides venezuelensis

Site-directed Mutagenesis of the Basic N-terminal Cluster of Pancreatic Bile Salt-dependent Lipase

Lectin-like Ox-LDL Receptor Is Expressed in Human INT-407 Intestinal Cells: Involvement in the Transcytosis of Pancreatic Bile Salt–dependent Lipase

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