Scavenger receptor class B type I reduces cholesterol absorption in cultured enterocyte CaCo-2 cells

Cai, Lei; Eckhardt, Erik; Shi, Wei; Zhao, Zhenze; Nasser, Munira; Villiers, Willem J.S. de; Westhuyzen, Deneys R. van der

doi:10.1194/jlr.m300303-jlr200

Cited by 55 publications

(41 citation statements)

References 56 publications

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“…Other transporters, such as scavenger receptor class B type I (SR-BI), which is localized both at the apical and basolateral membranes of enterocytes (27), have also been suspected of having a role in the control of cholesterol absorption. The possibility that SR-BI is a cholesterol transporter is suggested by the observation that intestine-specific overexpression of SR-BI in mice leads to an increase in cholesterol and TAG absorption in short-term absorption experiments (17).…”

Section: Cholesterolmentioning

confidence: 99%

Intestinal lipid absorption

Iqbal¹,

Hussain²

2009

American Journal of Physiology-Endocrinology and Metabolism

664

484

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Our knowledge of the uptake and transport of dietary fat and fat-soluble vitamins has advanced considerably. Researchers have identified several new mechanisms by which lipids are taken up by enterocytes and packaged as chylomicrons for export into the lymphatic system or clarified the actions of mechanisms previously known to participate in these processes. Fatty acids are taken up by enterocytes involving protein-mediated as well as proteinindependent processes. Net cholesterol uptake depends on the competing activities of NPC1L1, ABCG5, and ABCG8 present in the apical membrane. We have considerably more detailed information about the uptake of products of lipid hydrolysis, the active transport systems by which they reach the endoplasmic reticulum, the mechanisms by which they are resynthesized into neutral lipids and utilized within the endoplasmic reticulum to form lipoproteins, and the mechanisms by which lipoproteins are secreted from the basolateral side of the enterocyte. apoB and MTP are known to be central to the efficient assembly and secretion of lipoproteins. In recent studies, investigators found that cholesterol, phospholipids, and vitamin E can also be secreted from enterocytes as components of high-density apoB-free/apoAI-containing lipoproteins. Several of these advances will probably be investigated further for their potential as targets for the development of drugs that can suppress cholesterol absorption, thereby reducing the risk of hypercholesterolemia and cardiovascular disease.intestine; dietary fat; triacylglycerol; cholesterol; phospholipids; fat-soluble vitamins; microsomal triglyceride transfer protein DIETARY FATS CONSIST OF A WIDE ARRAY of polar and nonpolar lipids (32, 33). Triacylglycerol (TAG) is the dominant fat in the diet, contributing 90 -95% of the total energy derived from dietary fat. Dietary fats also include phospholipids (PLs), sterols (e.g., cholesterol), and many other lipids (e.g., fatsoluble vitamins). The predominant PL in the intestinal lumen is phosphatidylcholine (PC), which is derived mostly from bile (10 -20 g/day in humans) but also from the diet (ϳ1-2 g/day). The predominant dietary sterols are cholesterol (mostly of animal origin) and ␤-sitosterol (the major plant sterol). Although ␤-sitosterol accounts for 25% of dietary sterols, it is not absorbed by humans under physiological conditions.Researchers have been investigating the various steps involved in lipid digestion, absorption, and metabolism to identify factors that could serve as targets for the development of drugs capable of reducing the risk of lipid-associated disorders, including dyslipidemias and cardiovascular disease. In so doing, they have explored key aspects of lipid digestion hydrolysis, emulsification, and micelle formation. They have also explored key issues of absorption, e.g., the uptake of the products of lipid hydrolysis by enterocytes (the epithelial cells lining the walls of the intestinal lumen) and their transport to intracellular compartments, where fatty acids and sterols are...

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Section: Cholesterolmentioning

confidence: 99%

Intestinal lipid absorption

Iqbal¹,

Hussain²

2009

American Journal of Physiology-Endocrinology and Metabolism

664

484

View full text Add to dashboard Cite

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“…For SR-BI overexpression, cells were plated in 12-well plates and once 70% to 80% confluent, were transduced with adenovirus containing SR-BI vector (Ad-SRBI) 7 or empty vector (Ad-Null) at a multiplicity of infection of 20 in full medium for 18 hours. After 18 hours, medium was replaced with fresh medium and cells were used for experiments.…”

Section: Cells and Treatmentsmentioning

confidence: 99%

“…5,6 In polarized cells, SR-BI is known to be localized largely at the plasma membrane, either apically (eg, enterocytes 7 ) or basolaterally (eg, hepatocytes 8 and MadinDarby canine kidney [MDCK] cells 9 ). Several reports have indicated that SR-BI functions as an endocytic receptor, particularly in polarized cells such as hepatocytes 8 and kidney (MDCK) 10 cells, and it has been proposed that selective lipid uptake from HDL occurs during SR-BI-mediated HDL recycling within cells.…”

mentioning

confidence: 99%

Phosphatidylinositol-3-Kinase Regulates Scavenger Receptor Class B Type I Subcellular Localization and Selective Lipid Uptake in Hepatocytes

Shetty

Eckhardt

Post

et al. 2006

ATVB

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Objective-The high-density lipoprotein (HDL) receptor scavenger receptor Class B type I (SR-BI) plays a key role in mediating the final step of reverse cholesterol transport. This study examined the possible regulation of hepatic SR-BI by phosphatidylinositol-3-kinase (PI3K), a well known regulator of endocytosis and membrane protein trafficking. Methods and Results-SR-BI-dependent HDL selective cholesterol ester uptake in human HepG2 hepatoma cells was decreased (Ϸ50%) by the PI3K inhibitors wortmannin and LY294002. Insulin increased selective uptake (Ϸ30%), and this increase was blocked by PI3K inhibitors. Changes in SR-BI activity could be accounted for by pronounced changes in the subcellular localization and cell surface expression of SR-BI as determined by HDL cell surface binding, receptor biotinylation studies, and confocal fluorescence microscopy of HepG2 cells expressing green fluorescent protein-tagged SR-BI. Thus, under conditions of PI3K activation by insulin, and to a lesser extent by the SR-BI ligand HDL, cell surface expression of SR-BI was promoted, resulting in increased SR-BI-mediated HDL selective lipid uptake. Conclusion-Our

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“…Lipoproteins were double labeled by iodination of the protein component (31) and tracing the CE with nonhydrolyzable, intra- (32). Briefly, [1 ␣ ,2 ␣ (n) 3 H]cholesteryl oleyl ether suspended in dichloromethane was coated onto the inside of a glass tube by evaporation under nitrogen.…”

Section: Radiolabeling Of Lipoproteinsmentioning

confidence: 99%

ApoA-II modulates the association of HDL with class B scavenger receptors SR-BI and CD36

Beer

Castellani

Cai

et al. 2004

Journal of Lipid Research

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The class B scavenger receptors SR-BI and CD36 exhibit a broad ligand binding specificity. SR-BI is well characterized as a HDL receptor that mediates selective cholesteryl ester uptake from HDL. CD36, a receptor for oxidized LDL, also binds HDL and mediates selective cholesteryl ester uptake, although much less efficiently than SR-BI. Apolipoprotein A-II (apoA-II), the second most abundant HDL protein, is considered to be proatherogenic, but the underlying mechanisms are unclear. We previously showed that apoA-II modulates SR-BI-dependent binding and selective uptake of cholesteryl ester from reconstituted HDL. To investigate the effect of apoA-II in naturally occurring HDL on these processes, we compared HDL without apoA-II (from apoA-II null mice) with HDLs containing differing amounts of apoA-II (from C57BL/6 mice and transgenic mice expressing a mouse apoA-II transgene). The level of apoA-II in HDL was inversely correlated with HDL binding and selective cholesteryl ester uptake by both scavenger receptors, particularly CD36. Interestingly, for HDL lacking apoA-II, the efficiency with which CD36 mediated selective uptake reached a level similar to that of SR-BI. These results demonstrate that apoA-II exerts a marked effect on HDL binding and selective lipid uptake by the class B scavenger receptors and establishes a potentially important relationship between apoA-II and CD36.

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Scavenger receptor class B type I reduces cholesterol absorption in cultured enterocyte CaCo-2 cells

Cited by 55 publications

References 56 publications

Intestinal lipid absorption

Intestinal lipid absorption

Phosphatidylinositol-3-Kinase Regulates Scavenger Receptor Class B Type I Subcellular Localization and Selective Lipid Uptake in Hepatocytes

ApoA-II modulates the association of HDL with class B scavenger receptors SR-BI and CD36

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