Scavenger receptor class B member 1 protein: hepatic regulation and its effects on lipids, reverse cholesterol transport, and atherosclerosis

Kent, Anthony P.; Stylianou, Ioannis M.

doi:10.2147/hmer.s7860

Cited by 12 publications

(9 citation statements)

References 139 publications

(178 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The SR-BI receptor is associated with lipid metabolism and participates in the bidirectional transport of cholesterol between cells and HDL. Increased clearance of HDL-CE from plasma and enhanced reverse cholesterol transport have been shown to significantly reduce atherosclerosis in animal models[ 23 ]. Previous studies have confirmed that the extracellular domain of SR-BI is critical for its receptor function[ 19 ].…”

Section: Discussionmentioning

confidence: 99%

“…Currently, few reports on virus entry and host genomic SNPs have been published[ 22 ]. For SR-BI, researchers have focused on its regulation of HDL-cholesterol and other metabolites, and a very recent report showed that polymorphisms in the SR-BI gene are associated with the virological response in HCV-infected patients[ 23 , 24 ]. According to the results of a GWAS (genome-wide association study) of 10000 individuals, SNPs in the SR-BI gene are associated with a small, but significant elevation in plasma HDL-cholesterol levels[ 25 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Single amino acid mutation of SR-BI decreases infectivity of hepatitis C virus derived from cell culture in a cell culture model

Gao

et al. 2017

WJG

View full text Add to dashboard Cite

AIMTo investigate the effect of a single amino acid mutation in human class B scavenger receptor I (SR-BI) on the infectivity of cell culture-derived hepatitis C virus (HCVcc) in SR-BI knock-down Huh7-siSR-BI cells.METHODSSite-directed mutagenesis was used to construct the SR-BI S112F mutation, and the mutation was confirmed by nucleotide sequencing. SR-BI knock-down Huh7-siSR-BI cells were transfected with SR-BI S112F, SR-BI wild type (WT) and control plasmids, and then infected with HCVpp (HCV pseudoparticles) and hepatitis C virus derived from cell culture (HCVcc). A fluorescence assay was performed to analyze the effect of the S112F mutation on HCV entry; quantitative real-time PCR, immunofluorescence, and Western blot assays were used to analyze the effect of the S112F mutation on HCV infectivity. CHO cells expressing WT and SR-BI S112F were incubated with the HCV E2 protein expressed in HEK 293T cells, and flow cytometry was performed to examine the ability of SR-BI S112F to bind to the HCV E2 protein. Huh7-siSR-BI cells were transfected with SR-BI WT and the S112F mutant, and then DiI-HDL was added and images captured under the microscope to assess the ability of SR-BI S112F to take up HDL.RESULTSThe SR-BI S112F mutation was successfully constructed. The S112F mutation decreased the expression of the SR-BI mRNA and protein. SR-BI S112F decreased HCV entry and HCVcc infectivity in Huh7-siSR-BI cells. The S112F mutation impaired the binding of SR-BI to HCV E2 protein and decreased the HDL uptake of SR-BI.CONCLUSIONThe S112F single amino acid mutation in SR-BI decreased the levels of the SR-BI mRNA and protein, as well as the ability of SR-BI to bind to the HCV E2 protein. Amino acid 112 in SR-BI plays important roles in HCV entry and the infectivity of HCVcc in vitro.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Single amino acid mutation of SR-BI decreases infectivity of hepatitis C virus derived from cell culture in a cell culture model

Gao

et al. 2017

WJG

View full text Add to dashboard Cite

show abstract

“…Because the effect of SR-BI protein was independent of HDL-C levels 24 , the non-lipid pathways, such as affecting endothelial function 25 or inflammatory pathways 26 , have been hypothesized to be the functional mechanisms of rs10846744 variant. Interestingly, recent studies also demonstrated an interaction between glucose metabolism and the expression of SR-BI 27 28 through a transcriptional regulatory mechanism 29 30 . In comparison with the euglycemic control rats, administration of glucose could significantly decrease the hepatic expression of SR-BI in diabetic rats 29 30 .…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, recent studies also demonstrated an interaction between glucose metabolism and the expression of SR-BI 27 28 through a transcriptional regulatory mechanism 29 30 . In comparison with the euglycemic control rats, administration of glucose could significantly decrease the hepatic expression of SR-BI in diabetic rats 29 30 . In our study, we found that the rs10846744 GG genotype was significantly associated with a higher fasting blood glucose level in subjects with HCV infection, but not in controls.…”

Section: Discussionmentioning

confidence: 99%

Association of SCARB1 Gene Polymorphisms with Virological Response in Chronic Hepatitis C Patients Receiving Pegylated Interferon plus Ribavirin Therapy

Hsu

Liu

et al. 2016

Sci Rep

View full text Add to dashboard Cite

The scavenger receptor type B class I(SR-BI) is a receptor for high-density lipoproteins(HDL) and one of entry factors for hepatitis C virus(HCV). We examined the association of single nucleotide polymorphisms(SNPs) of the SCARB1 gene, which encodes SR-BI, with virologic responses to pegylated interferon-based treatment in Asian chronic hepatitis C(CHC) patients. Human genomic and clinical data were collected from 156 consecutive Taiwanese HCV genotype 1 or 2 patients who received pegylated interferon plus ribavirin therapy and 153 non-HCV healthy subjects. Three SNPs(rs10846744, rs5888, and rs3782287) of the SCARB1 gene that have been linked to humans diseases were investigated. rs10846744 rather than rs5888 or rs3782287 was associated with serum HCV RNA level and sustained virologic response(SVR) to pegylated interferon plus ribavirin therapy in CHC patients(GG vs. non-GG genotype, Adjusted Odds Ratio, 95% CI: 0.32, 0.11–0.95, P = 0.039). Among patients with IL28B rs8099917 non-TT genotypes, those with rs10846744 non-GG genotype had a higher SVR rate than those with GG genotypes. In addition, patients with GG genotype had a higher fasting blood glucose level than those with CC genotype. In conclusion, SCARB1 gene polymorphisms may serve as a potential predictor of treatment responses in CHC patients receiving interferon-based therapy. (ClinicalTrials.gov number, NCT02714712).

show abstract

“…As expected, less selective cholesteryl ester uptake from HDL particles (~20 %) is found in the liver of cholesteryl ester transfer protein (CETP)-expressing animals (Goldberg et al 1991 ). Hepatic SR-BI expression is regulated by dietary, hormonal, and pharmacological interventions; for reviews see (Kent and Stylianou 2011 ) (Landschulz et al 1996 ; Fluiter et al 1998 ; Serougne et al 1999 ).…”

Section: Introductionmentioning

confidence: 99%

Differential basolateral–apical distribution of scavenger receptor, class B, type I in cultured cells and the liver

Fruhwürth

Kovacs²,

Bittman

et al. 2014

Histochem Cell Biol

View full text Add to dashboard Cite

The high-density lipoprotein (HDL) receptor, scavenger receptor class B, type I (SR-BI), mediates selective cholesteryl ester uptake into the liver, which finally results in cholesterol secretion into the bile. Despite several reports, the distribution of hepatic SR-BI between the sinusoidal and canalicular membranes is still under debate. We present immunohistological data using specific markers showing that the bulk of SR-BI is present in sinusoidal membranes and, to a lesser extent, in canalicular membranes in murine and human liver sections. In addition, SR-BI was detected in preparations of rat liver canalicular membranes. We also compared the in vivo findings to HepG2 cells, a widely used in vitro hepatocyte model. Interestingly, SR-BI was enriched in bile canalicular-like (BC-like) structures in polarized HepG2 cells, which were cultivated either conventionally to form a monolayer or in Matrigel to form three-dimensional structures. Fluorescently labeled HDL was transported into close proximity of BC-like structures, whereas HDL labeled with the fluorescent cholesterol analog BODIPY-cholesterol was clearly detected within these structures. Importantly, similarly to human and mouse liver, SR-BI was localized in basolateral membranes in three-dimensional liver microtissues from primary human liver cells. Our results demonstrate that SR-BI is highly enriched in sinusoidal membranes and is also found in canalicular membranes. There was no significant basolateral–apical redistribution of hepatic SR-BI in fasting and refeeding experiments in mice. Furthermore, in vitro studies in polarized HepG2 cells showed explicit differences as SR-BI was highly enriched in BC-like structures. These structures are, however, functional and accumulated HDL-derived cholesterol. Thus, biological relevant model systems should be employed when investigating SR-BI distribution in vitro.Electronic supplementary materialThe online version of this article (doi:10.1007/s00418-014-1251-9) contains supplementary material, which is available to authorized users.

show abstract

Scavenger receptor class B member 1 protein: hepatic regulation and its effects on lipids, reverse cholesterol transport, and atherosclerosis

Cited by 12 publications

References 139 publications

Single amino acid mutation of SR-BI decreases infectivity of hepatitis C virus derived from cell culture in a cell culture model

Single amino acid mutation of SR-BI decreases infectivity of hepatitis C virus derived from cell culture in a cell culture model

Association of SCARB1 Gene Polymorphisms with Virological Response in Chronic Hepatitis C Patients Receiving Pegylated Interferon plus Ribavirin Therapy

Differential basolateral–apical distribution of scavenger receptor, class B, type I in cultured cells and the liver

Contact Info

Product

Resources

About