Identification of a Receptor Mediating Absorption of Dietary Cholesterol in the Intestine

Häuser, H.; Dyer, James H.; Nandy, Andreas; Vega, Miguel A.; Werder, Moritz; Bieliauskaite, Egle; Weber, Franz E.; Compassi, Sabina; Gemperli, Anja C.; Boffelli, Dario; Wehrli, E.; Schulthess, G; Phillips, Michael C.

doi:10.1021/bi982404y

Cited by 236 publications

(223 citation statements)

References 38 publications

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“…Geneticin and Opti-MEM were from Life Technologies, Inc., and isotonic Ficoll was from Amersham Pharmacia Biotech. The polyclonal anti-human SR-BI antibody against the extracellular loop of human SR-BI was raised in goat as described previously (12) and purified using a Sepharose G column (MabTrap ® GII, Amersham Pharmacia Biotech). Apoprotein A-I (apoAI) was prepared as described previously (12).…”

Section: Methodsmentioning

confidence: 99%

“…In contrast, a single band with an apparent molecular mass of 82 kDa was observed in the solubilized monocytes and neutrophils. Caco-2 cells and brush border membrane vesicles (BBMV) were used as a positive control yielding a single band at 84 kDa previously assigned to SR-BI (12). The differences in the molecular weight of SR-BI between the cell types are likely due to different cell specific glycosylation patterns.…”

Section: Sr-bi Mediates Phospholipid Import Into Monocytes-wementioning

confidence: 99%

“…The mechanisms mediating the selective phospholipid uptake are mostly unknown. Scavenger receptor BI (SR-BI), a cell membrane protein previously shown to mediate the selective uptake of cholesterol (9,10), could also be involved in the cellular incorporation of the phospholipids (11,12). In the present investigation, we studied the role of SR-BI for the selective phospholipid import into the cells.…”

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confidence: 99%

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Scavenger Receptor BI Transfers Major Lipoprotein-associated Phospholipids into the Cells

Urban¹,

Zieseniss²,

Werder³

et al. 2000

Journal of Biological Chemistry

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The phospholipids of lipoproteins can be transferred to cells by an endocytosis-independent uptake pathway. We analyzed the role of scavenger receptor BI (SR-BI) for the selective cellular phospholipid import. Human monocytes rapidly acquired the pyrene (py)-labeled phospholipids sphingomyelin (SM), phosphatidylcholine, and phosphatidylethanolamine from different donors (low and high density lipoproteins (LDL, HDL), lipid vesicles). The anti-SR-BI antibody directed against the extracellular loop of the membrane protein lowered the cellular import of the phospholipids by 40 -80%. The phospholipid transfer from the lipid vesicles into the monocytes was suppressed by LDL, HDL, and apoprotein AI. Transfection of BHK cells with the cDNA for human SR-BI enhanced the cellular import of the vesicle-derived py-phospholipids by 5-6-fold. In the case of the LDL donors, transfer of py-SM to the transfected cells was stimulated to a greater extent than the uptake of the other py-phospholipids. Similar differences were not observed when the vesicles and HDL were used as phospholipid donors. The concentration of LDL required for the half-maximal phospholipid import was close to the previously reported apparent dissociation constant for LDL binding to SR-BI. The low activation energy of the SR-BI-mediated py-phospholipid import indicated that the transfer occurs entirely in a hydrophobic environment. Disruption of cell membrane caveolae by cyclodextrin treatment reduced the SR-BIcatalyzed incorporation of py-SM, suggesting that intact caveolae are necessary for the phospholipid uptake. In conclusion, SR-BI mediates the selective import of the major lipoprotein-associated phospholipids into the cells, the transfer efficiency being dependent on the structure of the donor lipoprotein.Phospholipids are known to play essential roles in a multitude of cellular processes such as, for example, in intracellular signal transduction (1) and as cofactors of enzyme complexes mediating the proteolytic activation of coagulation proteins (2). Phospholipids are asymmetrically distributed over the two halves of cellular membranes, the asymmetry being generated by proteins catalyzing the transbilayer movement of the lipid molecules (3). Furthermore, there is also lateral separation of the phospholipids within the single monolayers. Indeed, the plasma membranes of many cells contain clusters of sphingolipids, cholesterol, and specific proteins known as caveolae and lipid rafts (4, 5). In order to maintain the physiologic intrabilayer and intramonolayer composition of the phospholipids, the influx and efflux of the phospholipids from the plasma membranes must be tightly regulated.The cellular uptake of phospholipids from extracellular donors is part of this regulatory system. In humans, plasma lipoproteins are a major extracellular source for phospholipids. By means of the endocytosis of low density lipoproteins (LDL), 1 cells also incorporate phospholipids. The capacity of different blood components to take up LDL particles by receptor-mediated en...

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Section: Methodsmentioning

confidence: 99%

Section: Sr-bi Mediates Phospholipid Import Into Monocytes-wementioning

confidence: 99%

mentioning

confidence: 99%

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Scavenger Receptor BI Transfers Major Lipoprotein-associated Phospholipids into the Cells

Urban¹,

Zieseniss²,

Werder³

et al. 2000

Journal of Biological Chemistry

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“…First, scavenger receptors, in general, have been shown to bind polysaccharides (Hampton et al, 1991). Second, class B scavenger receptors were located in intestine (Cai et al, 2001) where they catalyze cholesterol uptake (Hauser et al, 1998). Third, BSDL, which is involved in cholesterol absorption (Lombardo, 2001), is also susceptible to associate with lipoprotein structures such as LDL (Caillol et al, 1997), receptors of which are also expressed by intestinal cells (Fong et al, 1995).…”

Section: Lox-1 Implication In Bsdl Transcytosismentioning

confidence: 99%

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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“…As a multilipoprotein receptor, SCARB1 also regulates the concentrations of LDL-C and very-low-density lipoprotein (VLDL) (Acton et al 1996;Ueda et al 1999). Interestingly, SCARB1 is likely to be involved in intestinal absorption of TGs (Hauser et al 1998). Importantly, the SCARB1 gene is located on chromosome 12q24, a region showing significant linkage to plasma HDL-C and TG levels (Feitosa et al 2005).…”

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confidence: 99%

The SCARB1 gene is associated with lipid response to dietary and pharmacological interventions

et al. 2008

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The scavenger receptor class B type 1 (SCARB1) gene is a key component in the reverse cholesterol transport pathway and thus plays an important role in lipid metabolism. Studies suggest that the SCARB1 gene may contribute to variation in plasma lipid levels at fasting; however, the results have been inconsistent, and it is unclear whether SCARB1 may also influence lipid response to dietary and pharmacologic interventions. In this study, we examined genetic variation in the SCARB1 gene in participants of the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study for associations with basal lipid levels, changes in lipid measures after dietary fat intake, and fenofibrate treatment. We found that the exon 1 variant SCARB1_G2S was significantly associated with postfenofibrate change for triglycerides (TG) (P = 0.004). Subjects bearing SCARB1_G2S minor allele A tend to have higher responsiveness to fenofibrate in lowering TG. In summary, our study suggested that the SCARB1 gene may serve as a useful marker that predicts variation in baseline lipid levels, postprandial lipid response, and response to fenofibrate intervention.

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Identification of a Receptor Mediating Absorption of Dietary Cholesterol in the Intestine

Cited by 236 publications

References 38 publications

Scavenger Receptor BI Transfers Major Lipoprotein-associated Phospholipids into the Cells

Scavenger Receptor BI Transfers Major Lipoprotein-associated Phospholipids into the Cells

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

The SCARB1 gene is associated with lipid response to dietary and pharmacological interventions

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