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Mi-Hye Lee, Kathryn M Appleton, Hesham M El-Shewy, Mary G Sorci-Thomas, Michael J Thomas, Maria F Lopes-Virella, Louis M Luttrell, Samar M Hammad, Richard L Klein
HDL normally transports about 50-70% of plasma S1P and the S1P in HDL reportedly mediates several HDL-associated biological effects and signaling pathways. The HDL receptor, SR-BI, as well as the cell surface receptors for S1P (S1PRs) may be involved partially and/or completely in these HDL-induced processes. Here we investigate the nature of the HDL-stimulated interaction between the HDL receptor, SR-BI, and S1PR1 using a protein-fragment complementation assay (PCA) and confocal microscopy. In both primary rat aortic vascular smooth muscle (RVSMC) and HEK293 cells, the S1P content in HDL particles increased intracellular calcium concentration that was mediated by S1PR1...
November 23, 2016: Journal of Lipid Research
Herman J Kempen, Monica Gomaraschi, Sara Simonelli, Laura Calabresi, Matthijs Moerland, James Otvos, Elias Jeyarajah, David Kallend, Peter L J Wijngaard
BACKGROUND AND AIMS: Effects of single ascending doses of MDCO-216 on plasma lipid and lipoprotein levels were assessed in human healthy volunteers and in patients with stable coronary artery disease (CAD). METHODS: MDCO-216 was infused at a single dose of 5, 10, 20, 30 or 40 mg/kg over 2 h and blood was collected at 2, 4, 8, 24, 48, 168 and 720 h after start of infusion (ASOI). Lipoprotein lipids were assessed by FLPC and by 1H NMR. RESULTS: Plasma concentrations of free cholesterol (FC) displayed a rapid and dose-dependent rise, peaking at 8 h, but remaining above baseline until 48 h ASOI, whereas levels of esterified cholesterol (CE) increased at lower doses but not at higher doses, and even decreased below baseline at the highest dose...
October 24, 2016: Atherosclerosis
Akemi Kakino, Yoshiko Fujita, Atsushi Nakano, Sayaka Horiuchi, Tatsuya Sawamura
BACKGROUND: Modified low-density lipoprotein (LDL) binding to scavenger receptors has been implicated in atherosclerosis. It is hypothesized that a third molecule may affect modified LDL binding, therefore, this study focuses on the soluble endogenous protein, developmental endothelial locus-1 (Del-1), as an inhibitor of oxidized LDL (oxLDL) interactions.Methods and Results:Del-1 preferentially bound oxLDL over native LDL in a cell-free binding assay. Del-1 also inhibited DiI-labeled oxLDL uptake by scavenger receptors irrespective of the receptor type (LOX-1, SR-AI, CD36, or SR-BI) expressed in COS-7 cells, and independent of cell type (human coronary artery endothelial cells (HCAECs) or THP-1-derived macrophages)...
October 26, 2016: Circulation Journal: Official Journal of the Japanese Circulation Society
Jorge L Gutierrez-Pajares, Céline Ben Hassen, Stéphan Chevalier, Philippe G Frank
Studies have demonstrated the significant role of cholesterol and lipoprotein metabolism in the progression of cancer. The SCARB1 gene encodes the scavenger receptor class B type I (SR-BI), which is an 82-kDa glycoprotein with two transmembrane domains separated by a large extracellular loop. SR-BI plays an important role in the regulation of cholesterol exchange between cells and high-density lipoproteins. Accordingly, hepatic SR-BI has been shown to play an essential role in the regulation of the reverse cholesterol transport pathway, which promotes the removal and excretion of excess body cholesterol...
2016: Frontiers in Pharmacology
Demin Cai, Mengjie Yuan, Haoyu Liu, Shifeng Pan, Wenqiang Ma, Jian Hong, Ruqian Zhao
Betaine serves as an animal and human nutrient which has been heavily investigated in glucose and lipid metabolic regulation, yet the underlying mechanisms are still elusive. In this study, feeding sows with betaine-supplemented diets during pregnancy and lactation increased cholesterol content and low-density lipoprotein receptor (LDLR) and scavenger receptor class B type I (SR-BI) gene expression, but decreasing bile acids content and cholesterol-7a-hydroxylase (CYP7a1) expression in the liver of weaning piglets...
October 18, 2016: Nutrients
Anita Giglio, Anna Ammendola, Silvia Battistella, Attilio Naccarato, Alberto Pallavicini, Enrico Simeon, Antonio Tagarelli, Piero Giulio Giulianini
Honeybees have become important tools for the ecotoxicological assessment of soil, water and air metal contamination due to their extraordinary capacity to bioaccumulate toxic metals from the environment. The level of heavy metal pollution in the Trieste city was monitored using foraging bees of Apis mellifera ligustica from hives owned by beekeepers in two sites strategically located in the suburban industrial area and urban ones chosen as control. The metal concentration in foraging bees was determined by inductively coupled plasma-mass spectrometry...
October 15, 2016: Environmental Science and Pollution Research International
Tiantian Luo, Jing Hu, Dan Xi, Haowei Xiong, Wenshuai He, Jichen Liu, Menghao Li, Hao Lu, Jinzhen Zhao, Wenyan Lai, Zhigang Guo
Previously, we reported that heat shock protein (HSP)65 impairs the effects of high-density lipoprotein on macrophages. We also showed that immune response activation adversely affects reverse cholesterol transport (RCT). In this study, we investigated the effects of the Src family kinase lymphocyte-specific protein tyrosine kinase (Lck) and elucidated the mechanism underlying HSP65-regulated cholesterol efflux in T cells. We evaluated cell proliferation, Lck expression, and inflammatory cytokine production in Jurkat cells and CD4(+) T cells...
October 14, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Maneesha A Rajora, Gang Zheng
Scavenger receptor class B type I (SR-BI) plays an important role in trafficking cholesteryl esters between the core of high density lipoprotein and the liver. Interestingly, this integral membrane protein receptor is also implicated in the metabolism of cholesterol by cancer cells, whereby overexpression of SR-BI has been observed in a number of tumors and cancer cell lines, including breast and prostate cancers. Consequently, SR-BI has recently gained attention as a cancer biomarker and exciting target for the direct cytosolic delivery of therapeutic agents...
2016: Frontiers in Pharmacology
Susanne Pfeiler, Avinash B Khandagale, Astrid Magenau, Maryana Nichols, Harry F G Heijnen, Franz Rinninger, Tilman Ziegler, Stephanie Seveau, Sören Schubert, Stefan Zahler, Admar Verschoor, Eicke Latz, Steffen Massberg, Katharina Gaus, Bernd Engelmann
The mechanisms protecting from immunopathology during acute bacterial infections are incompletely known. We found that in response to apoptotic immune cells and live or dead Listeria monocytogenes scavenger receptor BI (SR-BI), an anti-atherogenic lipid exchange mediator, activated internalization mechanisms with characteristics of macropinocytosis and, assisted by Golgi fragmentation, initiated autophagic responses. This was supported by scavenger receptor-induced local increases in membrane cholesterol concentrations which generated lipid domains particularly in cell extensions and the Golgi...
October 3, 2016: Scientific Reports
Rinku Pal, Qingen Ke, German A Pihan, Ayce Yesilaltay, Marsha L Penman, Li Wang, Chandramohan Chitraju, Peter M Kang, Monty Krieger, Olivier Kocher
The HDL receptor SR-BI mediates the transfer of cholesteryl esters from HDL to cells and controls HDL abundance and structure. Depending on the genetic background, loss of SR-BI causes hypercholesterolemia, anemia, reticulocytosis, splenomegaly, thrombocytopenia, female infertility and fatal coronary heart disease (CHD). The C-terminus of SR-BI (505QEAKL509) must bind to the cytoplasmic adaptor PDZK1 for normal hepatic -but not steroidogenic cell- expression of SR-BI protein. To determine if SR-BI's C-terminus is also required for normal protein levels in steroidogenic cells, we introduced into SR-BI's gene a 507Ala/STOP mutation that produces a truncated receptor (SR-BIΔCT)...
September 30, 2016: American Journal of Physiology. Heart and Circulatory Physiology
Fang Zhang, Catherine Sodroski, Helen Cha, Qisheng Li, T Jake Liang
BACKGROUND & AIMS: The signaling molecule and transcriptional regulator SMAD6, which inhibits the transforming growth factor β signaling pathway, is required for infection of hepatocytes by hepatitis C virus (HCV). We investigated the mechanisms by which SMAD6, and another inhibitory SMAD (SMAD7), promote HCV infection in human hepatoma cells and hepatocytes. METHODS: We infected Huh7 and Huh7.5.1 cells and primary human hepatocytes with JFH1 HCVcc; we measured HCV binding, intracellular levels of HCV RNA, and expression of target genes...
September 30, 2016: Gastroenterology
Tanja Eberhart, Karin Eigner, Yüksel Filik, Stefanie Fruhwürth, Herbert Stangl, Clemens Röhrl
Scavenger receptor class B, type I (SR-BI) is the main receptor for high-density lipoprotein (HDL) and an emerging atheroprotective candidate. A central function of SR-BI is the delivery of HDL-derived cholesterol to the liver for subsequent excretion into the bile. Here, we investigated the regulation of SR-BI by the unfolded protein response (UPR), an adaptive mechanism induced by endoplasmic reticulum (ER) stress, which is frequently activated in metabolic disorders. We provide evidence that induction of acute ER stress by well-characterized chemical inducers leads to decreased SR-BI expression in hepatocyte-derived cell lines...
October 21, 2016: Biochemical and Biophysical Research Communications
Adam Zuiani, Kevin Chen, Megan C Schwarz, James P White, Vincent C Luca, Daved H Fremont, David Wang, Matthew J Evans, Michael S Diamond
: While natural hepatitis C virus (HCV) infection results in highly diverse quasispecies of related viruses over time, mutations accumulate more slowly in tissue culture, in part because of the inefficiency of replication in cells. To create a highly diverse population of HCV particles in cell culture and identify novel growth-enhancing mutations, we engineered a library of infectious HCV with all codons represented at most positions in the ectodomain of the E2 gene. We identified many putative growth-adaptive mutations and selected nine highly represented E2 mutants for further study: Q412R, T416R, S449P, T563V, A579R, L619T, V626S, K632T, and L644I...
December 1, 2016: Journal of Virology
Wei Guo, Chunying Jiang, Liu Yang, Tianqi Li, Xia Liu, Mengxia Jin, Kai Qu, Huili Chen, Xiangju Jin, Hongyue Liu, Haibo Zhu, Yinghong Wang
Atherosclerosis (AS) is a progressive disease that contributes to cardiovascular disease and shows a complex etiology, including genetic and environmental factors. To understand systemic metabolic changes and to identify potential biomarkers correlated with the occurrence and perpetuation of diet-induced AS, we applied (1)H NMR-based metabolomics to detect the time-related metabolic profiles of plasma, urine, and liver extracts from male hamsters fed a high fat and high cholesterol (HFHC) diet. Conventional biochemical assays and histopathological examinations as well as protein expression analyses were performed to provide complementary information...
October 7, 2016: Journal of Proteome Research
Ching-Sheng Hsu, Shih-Jer Hsu, Wei-Liang Liu, Ding-Shinn Chen, Jia-Horng Kao
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...
2016: Scientific Reports
Kailash Gulshan, Gregory Brubaker, Heather Conger, Shuhui Wang, Renliang Zhang, Stanley L Hazen, Jonathan D Smith
RATIONALE: The molecular mechanism by which ATP-binding cassette transporter A1 (ABCA1) mediates cellular binding of apolipoprotein A-I (apoA1) and nascent high-density lipoprotein (HDL) assembly is not well understood. OBJECTIVE: To determine the cell surface lipid that mediates apoA1 binding to ABCA1-expressing cells and the role it plays in nascent HDL assembly. METHODS AND RESULTS: Using multiple biochemical and biophysical methods, we found that apoA1 binds specifically to phosphatidylinositol (4,5) bis-phosphate (PIP2)...
September 16, 2016: Circulation Research
Hui Gao, Lingyan Li, Lan Li, Bo Gong, Pengzhi Dong, Patrick Asare Fordjour, Yan Zhu, Guanwei Fan
Contemporary research suggests that macrophage foam cell and cholesterol efflux defect play pivotal role in atherogenesis. We reported on the heretofore unknown therapeutic effect of Danshensu (DSS) in reducing intracellular cholesterol level and unraveled the mechanism of DSS promotes cholesterol efflux. Oxidized low-density lipoprotein stimulation of Raw264.7 cells into foam cells, which were treated with DSS and co-treated with Simvastatin and Rosiglitazone. PPARγ, ABCA1, ABCG1, SR-BI, CD36, and LXR-α mRNA were quantified by Real-Time PCR...
September 2016: Lipids
Zeina Soayfane, François Tercé, Michela Cantiello, Horst Robenek, Michel Nauze, Valérie Bézirard, Sophie Allart, Bruno Payré, Florence Capilla, Christel Cartier, Christine Peres, Talal Al Saati, Vassilia Théodorou, David W Nelson, Chi-Liang Eric Yen, Xavier Collet, Christine Coméra
BACKGROUND: Intestinal absorption of dietary lipids involves their hydrolysis in the lumen of proximal intestine as well as uptake, intracellular transport and re-assembly of hydrolyzed lipids in enterocytes, leading to the formation and secretion of the lipoproteins chylomicrons and HDL. In this study, we examined the potential involvement of cytosolic lipid droplets (CLD) whose function in the process of lipid absorption is poorly understood. METHODS: Intestinal lipid absorption was studied in mouse after gavage...
2016: Nutrition & Metabolism
Guohua Song, Xia Wu, Pu Zhang, Yang Yu, Mingfeng Yang, Peng Jiao, Ni Wang, Haiming Song, You Wu, Xiangjian Zhang, Huaxia Liu, Shucun Qin
Endoplasmic reticulum stress (ERS) in adipocytes can modulate adipokines secretion. The aim of this study was to explore the protective effect of high-density lipoprotein (HDL) on oxidized low-density lipoprotein (ox-LDL)-induced ERS-C/EBP homologous protein (CHOP) pathway-mediated adipokine secretion. Our results showed that serum adipokines, including visfatin, resistin and TNF-α, correlated inversely with serum HDL cholesterol level in patients with abdominal obesity. In vitro, like ERS inhibitor 4-phenylbutyric acid (PBA), HDL inhibited ox-LDL- or tunicamycin (TM, an ERS inducer)-induced increase in visfatin and resistin secretion...
2016: Scientific Reports
Shizuya Yamashita, Yuji Matsuzawa
PURPOSE OF REVIEW: To re-evaluate the functions of plasma cholesteryl ester transfer protein (CETP) in atherosclerosis based upon recent findings from human genetics and pharmacological CETP manipulation. RECENT FINDINGS: CETP is involved in the transfer of cholesteryl ester from HDL to apolipoprotein B-containing lipoproteins, a key step of reverse cholesterol transport (RCT). CETP inhibitors have been developed to raise serum HDL-cholesterol (HDL-C) levels and reduce cardiovascular events...
October 2016: Current Opinion in Lipidology
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