The Role of Human and Mouse Hepatic Scavenger Receptor Class B Type I (SR-BI) in the Selective Uptake of Low-Density Lipoprotein−Cholesteryl Esters

Rhainds, David; Brodeur, Mathieu R.; Lapointe, Jany; Charpentier, Daniel; Falstrault, Louise; Brissette, Louise

doi:10.1021/bi026949a

Cited by 58 publications

(39 citation statements)

References 73 publications

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“…We found that SR-BI is recovered in Triton X-100 soluble fractions of HepG2 cells (Rhainds et al, 2003). It is worth noting that a concentration of Triton X-100 as low as 0.25% was sufficient to solubilize >80% of SR-BI in HepG2 cells and that SR-BI in the Triton X-100 insoluble fraction was detectable only in HepG2 cells extracted with 0.1% Triton X-100 (data not shown).…”

Section: Discussionmentioning

confidence: 72%

“…Our results show that CE selective uptake from LDL, which is a SR-BI-dependent pathway in HepG2 cells Rhainds et al, 2003), was sensitive to enzymatic disruption of rafts structure by either COase, SMase or to sequestration of membrane cholesterol by filipin III treatment. Surprisingly, CE selective uptake from HDL3 increased with COase, SMase and β-CD.…”

Section: Discussionmentioning

confidence: 74%

“…Differences were considered significant at P<0.05. (Rhainds et al, 2003), however caveolin-1 expression in this cell type is uncertain. Our first aim was to determine if SR-BI resides in cholesterol and sphingomyelin-rich membrane rafts of HepG2 cells and if caveolin-1 is expressed and copurified with SR-BI in these cells.…”

Section: Lipoprotein Recycling (Retroendocytosis) Assaysmentioning

confidence: 98%

“…We have shown that SR-BI is the major receptor for CE selective uptake from LDL and HDL3 in HepG2 cells Rhainds et al, 2003) and that LDL-CE selective uptake brings regulatory cholesterol to HepG2 cells (Charest …”

Section: Introductionmentioning

confidence: 99%

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Localization and regulation of SR-BI in membrane rafts of HepG2 cells

Rhainds

Bourgeois

Bourret

et al. 2004

Journal of Cell Science

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The scavenger receptor class B, type I (SR-BI) mediates cholesteryl esters (CE) selective uptake from low density lipoprotein (LDL) and high-density lipoprotein (HDL) particles. In a number of tissues expressing caveolin, SR-BI is localized in caveolae. We show using detergent-free sucrose gradients that SR-BI is found in membrane rafts devoid of caveolin-1 in the human hepatoma HepG2 cell. Perturbation of the structure of HepG2 cell membrane rafts with cholesterol oxidase or sphingomyelinase decreased LDL-CE association due to selective uptake by 60%, while HDL3-CE selective uptake was increased 2.3-fold by cholesterol oxidase but was not affected by sphingomyelinase. Sequestration of membrane cholesterol with filipin III decreased LDL-CE selective uptake by 25%, while it had no effect on HDL3-CE selective uptake. Extraction of cell membrane cholesterol with β-cyclodextrin increased LDL- and HDL3-CE selective uptake by 1.6-fold and 3-fold, respectively. We found that CE-selective uptake from both HDL and LDL occurs by a pathway involving retro-endocytosis in HepG2 cells. An analysis of the effect of SR-BI level on the expression of critical lipid sensor and lipid binding proteins was conducted with stable transformants of HepG2 cell overexpressing SR-BI. We found that liver-type fatty acid binding protein expression level is higher in SR-BI-overexpressing cells and that caveolin-1 and sterol response element binding protein-2 levels are reduced. Thus, in this hepatic cell model, SR-BI is associated with membrane rafts devoid of caveolin and its expression affects intracellular lipid binding and lipid sensor proteins. SR-BI-dependent LDL- and HDL-CE selective uptake are affected differently by the integrity of membrane rafts, but both occur by a retroendocytic pathway in HepG2 cells.

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Section: Discussionmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 74%

Section: Lipoprotein Recycling (Retroendocytosis) Assaysmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Localization and regulation of SR-BI in membrane rafts of HepG2 cells

Rhainds

Bourgeois

Bourret

et al. 2004

Journal of Cell Science

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“…28 To establish whether scavenger receptors are involved, we incubated the hepatocyte-LSEC cocultures with a fivefold excess of unlabelled acLDL (100 g/mL). Figure 2A shows that the addition of acLDL did not interfere with the internalization of DiI-LDL by hepatocytes in cocultures, suggesting that the hepatic scavenger cell receptors are not involved in the upregulation of LDL uptake.…”

Section: Ldl Uptake In Hepatocyte Culture and Coculturementioning

confidence: 99%

Liver endothelial cells promote LDL-R expression and the uptake of HCV-like particles in primary rat and human hepatocytes

et al. 2006

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Low-density lipoprotein (LDL) is an important carrier of plasma cholesterol and triglycerides whose concentration is regulated by the liver parenchymal cells. Abnormal LDL regulation is thought to cause atherosclerosis, while viral binding to LDL has been suggested to facilitate hepatitis C infection. Primary hepatocytes quickly lose the ability to clear LDL during in vitro culture. Here we show that the coculture of hepatocytes with liver sinusoidal endothelial cells (LSEC) significantly increases the ability of hepatocytes to uptake LDL in vitro. LDL uptake does not increase when hepatocytes are cocultured with other cell types such as fibroblasts or umbilical vein endothelial cells. We find that LSECs induce the hepatic expression of the LDL receptor and the epidermal growth factor receptor. In addition, while hepatocytes in single culture did not take up hepatitis C virus (HCV)-like particles, the hepatocytes cocultured with LSECs showed a high level of HCV-like particle uptake. We suggest that coculture with LSECs induces the emergence of a sinusoidal surface in primary hepatocytes conducive to the uptake of HCV-like particles. In conclusion, our findings describe a novel model of polarized hepatocytes in vitro that can be used for the study of LDL metabolism and hepatitis C infection. L ow-density lipoprotein (LDL) is a plasma-carried particle whose lipid component includes cholesterol and triglycerides. 1 LDL originates from very low-density lipoprotein (vLDL) synthesized by the liver with apoprotein B-100. The vLDL is converted to LDL by an endothelial lipase, which releases free fatty acids, increasing the density of the particle to form LDL. Excess LDL is then taken up by hepatocytes through LDL receptor (LDL-R)-mediated endocytosis. 1 Improper hepatic clearance of LDL results in elevated plasma levels of LDL which is a serious risk factor for the development of atherosclerosis. 2 One of the first steps in atherosclerosis is the passage of LDL into the vascular wall. Once trapped in the vessel wall, LDL can undergo oxidation. 3 Oxidized LDL is no longer a ligand for the LDL receptor. 4 Accumulation of oxidized LDL and LDL aggregates in the vessel wall stimulates an inflammatory response causing endothelial injury, macrophage recruitment, foam cell formation, and smooth muscle cell proliferation. 3 Current therapeutic intervention includes administration of statins, which block cholesterol production and increase expression of the LDL-R by the liver parenchymal cells, 2 removing LDL from circulation. 5 In addition, liver sinusoidal endothelial cells (LSECs) remove oxidized LDL from the circulation via the scavenger cell receptor. 5 LDL-and LDL-R-mediated pathways have also been shown to play a role in hepatitis C virus (HCV) infection. 6 The HCV surface receptors, glycoproteins E1 and E2, have been shown to associate with LDL and vLDL. 7 The virus particle itself was shown to associate with the

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Enhancement of HDL Formation and Normalization of Intravascular HDL Remodeling

Kontush¹,

Chapman²

2011

High‐Density Lipoproteins

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The Role of Human and Mouse Hepatic Scavenger Receptor Class B Type I (SR-BI) in the Selective Uptake of Low-Density Lipoprotein−Cholesteryl Esters

Cited by 58 publications

References 73 publications

Localization and regulation of SR-BI in membrane rafts of HepG2 cells

Localization and regulation of SR-BI in membrane rafts of HepG2 cells

Liver endothelial cells promote LDL-R expression and the uptake of HCV-like particles in primary rat and human hepatocytes

Enhancement of HDL Formation and Normalization of Intravascular HDL Remodeling

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