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Syed Saad Hussain, Megan T Harris, Alex J B Kreutzberger, Candice M Inouye, Catherine A Doyle, Anna M Castle, Peter Arvan, J David Castle
In pancreatic β cells, insulin granule membranes are enriched in cholesterol and are both recycled and newly generated. Cholesterol's role in supporting granule membrane formation and function is poorly understood.<u>A</u>TP<u>b</u>inding<u>c</u>assette transporters ABCG1 and ABCA1 regulate intracellular cholesterol and are important for insulin secretion. RNAi-induced depletion in cultured pancreatic β cells shows that ABCG1 is needed to stabilize newly made insulin granules against lysosomal degradation; ABCA1 is also involved but to a lesser extent...
March 14, 2018: Molecular Biology of the Cell
Xiao Li, Jingting Guo, Ning Liang, Xinwei Jiang, Yuan Song, Shiyi Ou, Yunfeng Hu, Rui Jiao, Weibin Bai
Gingerols, the pungent ingredients in ginger, are reported to possess a cholesterol-lowering activity. However, the underlying mechanism remains unclear. The present study was to investigate how 6-gingerol (6-GN), the most abundant gingerol in fresh ginger, regulates hepatic cholesterol metabolism. HepG2 cells were incubated with various concentrations of 6-GN ranging from 50 to 200 μM for 24 h. Results showed that both cellular total cholesterol and free cholesterol decreased in a dose-dependent manner. Besides, 6-GN ranging from 100 to 200 μM increased the LDLR protein and uptake of fluorescent-labeled LDL...
2018: Frontiers in Pharmacology
Sarah E Kleinstein, Patrick R Shea, Andrew S Allen, David M Koelle, Anna Wald, David B Goldstein
Herpes simplex virus type 2 (HSV-2) is an incurable viral infection with severity ranging from asymptomatic to frequent recurrences. The viral shedding rate has been shown as a reproducible HSV-2 severity end point that correlates with lesion rates. We used a genome-wide association study (GWAS) to investigate the role of common human genetic variation in HSV-2 severity. We performed a GWAS on 223 HSV-2-positive participants of European ancestry. Severity was measured by viral shedding rate, as defined by the percent of days PCR+ for HSV-2 DNA over at least 30 days...
February 28, 2018: Genes and Immunity
Caixia Guo, Ru Ma, Xiaoying Liu, Tian Chen, Yang Li, Yang Yu, Junchao Duan, Xianqing Zhou, Yanbo Li, Zhiwei Sun
Oxidized low-density lipoprotein (oxLDL), a marker of hyperlipidemia, plays a pivotal role in the development of atherosclerosis through the induction of macrophage-derived foam cell formation and thereafter apoptosis. Previous studies have indicated that silica nanoparticle (SiNPs) may exert a proatherogenic role, which could induce endothelial dysfunction, and monocytes infiltration. However, little is known about SiNPs' effects on macrophage-derived foam cell formation and apoptosis in the pathogenesis of atherosclerosis...
March 10, 2018: Science of the Total Environment
Habib Ghaznavi, Ehsan Aali, Mohammad Soleiman Soltanpour
BACKGROUND: ATP - binding cassette transporter A1 (ABCA1) plays essential roles in the biogenesis of high -density lipoprotein - cholesterol. Variations in the ABCA1 gene may influence the risk of coronary artery disease (CAD). AIM: Present study aimed to investigate the association of rs2230806 (R219K) polymorphism of ABCA1 gene with the development and severity of CAD in an Iranian population. MATERIALS AND METHODS: Our study population consisted of 100 patients with angiographically confirmed CAD and 100 controls...
February 15, 2018: Open Access Macedonian Journal of Medical Sciences
Shuli Yang, Lihui Si, Limei Fan, Wenwen Jian, Huilin Pei, Ruixin Lin
Lycium barbarum L . (LBL) has beneficial effects on gestational diabetes mellitus (GDM) but the related mechanism remains unclear. Polysaccharides of LBL (LBLP) are the main bioactive components of LBL. miR-33, ATP-binding cassette transporter A1 (ABCA1) and sterol regulatory element-binding transcription 1 (SREBF1) affect lipid profiles, which are associated with GDM risk. LBLP may exert protective against GDM by affecting these molecules. Four LBLP fractions: LBLP-I, LBLP-II, LBLP-III, and LBLP-IV were isolated from LBL and further purified by using DEAE-Sephadex column...
2018: Frontiers in Endocrinology
Michelle S M A Damen, Jéssica Cristina Dos Santos, Rob Hermsen, J Adam van der Vliet, Mihai G Netea, Niels P Riksen, Charles A Dinarello, Leo A B Joosten, Bas Heinhuis
BACKGROUND AND AIMS: The role of interleukin (IL-)32 in inflammatory conditions is well-established, however, the mechanism behind its role in atherosclerosis remains unexplained. Our group reported a promoter single nucleotide polymorphism in IL-32 associated with higher high-density lipoprotein (HDL) concentrations. We hypothesize that endogenous IL-32 in liver cells, a human monocytic cell line and carotid plaque tissue, can affect atherosclerosis by regulating (HDL) cholesterol homeostasis via expression of cholesterol transporters/mediators...
March 2, 2018: Atherosclerosis
Claus Uhrenholt Christensen, Emilie Glavind, Karen Louise Thomsen, Yong Ook Kim, Sara Heebøll, Detlef Schuppan, Stephen Hamilton-Dutoit, Christian Würtz Heegaard, Henning Grønbæk
BACKGROUND AND AIMS: Hepatic cholesterol deposition drives inflammation and fibrosis in non-alcoholic steatohepatitis (NASH). The Niemann-Pick type C2 (NPC2) protein plays an important role in regulating intracellular cholesterol trafficking and homeostasis. We hypothesized that intravenous NPC2 supplementation reduces cholesterol accumulation, hepatic inflammation and fibrogenesis in a nutritional NASH rat model. METHODS: Rats were fed a high-fat, high-cholesterol (HFHC) diet for four weeks resulting in moderately severe NASH...
2018: PloS One
Jason S Hauptman, Robert Bollo, Rama Damerla, Brian Gibbs, Cecilia Lo, Aviva Katz, Stephanie Greene
Myelomeningocele and gastroschisis, on their own, are both relatively common entities encountered in pediatric surgical care. Coexistence of these pathologies, however, is exceedingly rare. The authors report on 2 patients who presented with myelomeningocele and gastroschisis at birth. They obtained blood for whole-exome analysis for one of the patients and identified 3 mutations that could be related to the underlying anomalies: homozygous mutations in FAM171B and ABCA1 and a hemizygous (X-linked) mutation in COL4A5...
March 9, 2018: Journal of Neurosurgery. Pediatrics
Masanori Tachikawa, Hidetoh Toki, Masahiko Watanabe, Masatoshi Tomi, Ken-Ichi Hosoya, Tetsuya Terasaki
The A-subclass of ATP-binding cassette (ABC) transporters is a highly conserved superfamily of potent lipid transporters. Although the ABCA1-like subgroup of ABCA1-4, and A7 have been shown to mediate the transport of endogenous lipids, the roles of the ABCA6-like subgroup transporters, which have been identified as a unique gene cluster on human chromosome 17q24 (ABCA5, A6, A8, A9, and A10) and mouse chromosome 11 (Abca5, a6, a8a, a8b, and a9), remains largely unknown. The purpose of the present study was to clarify the spatial and temporal expression profiles of Abca6-like subgroup transporters in embryonic and postnatal mouse brains by a combination of in situ hybridization and quantitative polymerase chain reaction (PCR) using magnetically isolated brain vascular endothelial cells...
March 8, 2018: Anatomical Science International
Chong Huang, Xiao-Hua Yu, Xi-Long Zheng, Xiang Ou, Chao-Ke Tang
Macrophage autophagy contributes to the hydrolysis of cholesteryl ester into free cholesterol mainly for ATP-binding cassette transporter A1 (ABCA1)-dependent efflux. Interferon-stimulated gene 15 (ISG15) has been shown to regulate autophagy in multiple types of cells. The present study aimed to examine the effects of ISG15 on autophagy and cholesterol efflux in THP-1 macrophage-derived foam cells and to explore the underlying molecular mechanisms. Our results showed that overexpression of ISG15 promoted autophagy and cholesterol efflux and inhibited lipid accumulation without impact on ABCA1 expression...
March 5, 2018: European Journal of Pharmacology
Hua Su, Chen Ye, Qian Wen, Hong-Yan Zhu, Li-Xia Yi, Chun Zhang
BACKGROUND: It is well-recognized that injection of iodinated radiographic contrast media (CM) sometimes causes acute renal injury via multiple mechanisms, such as vasoconstriction, toxicity on glomerular endothelium and tubular epithelium and so forth. CASE PRESENTATION: A 51-year-old man developed acute renal injury with proteinuria after CM administration. To our surprise, in his renal biopsy sample the myelin figure like structure was observed in glomerular endothelium and mesangial cells by transmission electron microscopy...
March 6, 2018: BMC Nephrology
Sadhbh O'Neill, Mette Bohl Larsen, Søren Gregersen, Kjeld Hermansen, Lorraine O'Driscoll
Due to increasing prevalence of obesity, a simple method or methods for the diagnosis of metabolic syndrome are urgently required to reduce the risk of associated cardiovascular disease, diabetes and cancer. This study aimed to identify a miRNA biomarker that may distinguish metabolic syndrome from obesity and to investigate if such a miRNA may have functional relevance for metabolic syndrome. 52 adults with clinical obesity (n=26) or metabolic syndrome (n=26) were recruited. Plasma specimens were procured from all and were randomly designated to discovery and validation cohorts...
February 6, 2018: Oncotarget
Yi Zeng, Yi Peng, Kun Tang, Yu Qin Wang, Zhe Yu Zhao, Xin Yu Wei, Xiao Le Xu
As the most abundant flavonoid in Ampelopsis grossedentata, the protective effects of dihydromyricetin on atherosclerosis have been well established, yet the detailed mechanisms are not fully understood. The aim of the present study was to examine the effect of dihydromyricetin on lipid accumulation and the underlying molecular mechanisms in macrophages and ApoE-/- mice. Incubation with dihydromyricetin significantly attenuated oxidized low-density lipoprotein (ox-LDL)-mediated cholesterol and lipid accumulation in THP-1-derived macrophages, which was due to increased cholesterol efflux...
March 2, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Hui Liang, Yutong Wang
Abnormal lipid metabolism may contribute to the pathogenesis of non-alcoholic steatohepatitis (NASH). The ATP-binding cassette transporter A1 (ABCA1) protein mediates the transport of cholesterol and phospholipids from cells to apolipoprotein A-I (apoA-I) to generate nascent HDL particles. Previous studies revealed that the overexpression of ABCA1 alleviated hepatic lipid levels by modifying lipid transport. Here, we examined the effect of berberine (BBR) on ABCA1 in QSG-7701 hepatocytes and in mice. BBR decreased hepatic cholesterol and triglyceride levels...
March 2, 2018: Biochemical and Biophysical Research Communications
Zulong Xie, Xuedong Wang, Xinxin Liu, Huaan Du, Changbin Sun, Xin Shao, Jiangtian Tian, Xia Gu, Hailong Wang, Jinwei Tian, Bo Yu
BACKGROUND: Obesity is causally associated with atherosclerosis, and adipose tissue (AT)-derived exosomes may be implicated in the metabolic complications of obesity. However, the precise role of AT-exosomes in atherogenesis remains unclear. We herein aimed to assess the effect of AT-exosomes on macrophage foam cell formation and polarization and subsequent atherosclerosis development. METHODS AND RESULTS: Four types of exosomes isolated from the supernatants of ex vivo subcutaneous AT and visceral AT (VAT) explants that were derived from wild-type mice and high-fat diet (HFD)-induced obese mice were effectively taken up by RAW264...
March 3, 2018: Journal of the American Heart Association
Xiao Huang, Pascale Anderle, Lu Hostettler, Marc U Baumann, Daniel V Surbek, Edgar C Ontsouka, Christiane Albrecht
BACKGROUND: Gestational disorders such as intrauterine growth restriction (IUGR) and pre-eclampsia (PE) are main causes of poor perinatal outcomes worldwide. Both diseases are related with impaired materno-fetal nutrient transfer, but the crucial transport mechanisms underlying IUGR and PE are not fully elucidated. In this study, we aimed to identify membrane transporters highly associated with transplacental nutrient deficiencies in IUGR/PE. RESULTS: In silico analyses on the identification of differentially expressed nutrient transporters were conducted using seven eligible microarray datasets (from Gene Expression Omnibus), encompassing control and IUGR/PE placental samples...
March 2, 2018: BMC Genomics
Jingjing Wang, Chong Xiao, Zhengkai Wei, Yanan Wang, Xu Zhang, Yunhe Fu
Liver X Receptors (LXRs) belong to the nuclear receptor superfamily, have been reported that activation of LXRs with synthetic ligands has anti-inflammatory effects in various inflammatory diseases. This study aims at investigating the effects of T0901317 (T0), a synthetic LXRs ligand, on lipopolysaccharide (LPS)-stimulated primary bovine mammary epithelial cells (bMECs). BMECs were stimulated by LPS in the presence or absence of T0. The results showed that treatment with T0 significantly inhibited LPS-induced tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) expression...
March 2018: Veterinary Immunology and Immunopathology
Ibragim Gaidarov, Todd Anthony, Joel Gatlin, Xiaohua Chen, David Mills, Michelle Solomon, Sangdon Han, Graeme Semple, David J Unett
GPR84 is an orphan G-protein coupled receptor, expressed on monocytes, macrophages and neutrophils and is significantly upregulated by inflammatory stimuli. The physiological role of GPR84 remains largely unknown. Medium chain fatty acids (MCFA) activate the receptor and have been proposed to be its endogenous ligands, although the high concentrations of MCFAs required for receptor activation generally exceed normal physiological levels. We identified the natural product embelin as a highly potent and selective surrogate GPR84 agonist (originally disclosed in patent application WO2007027661A2, 2007) and synthesized close structural analogs with widely varying receptor activities...
February 19, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Sang Bong Ahn, Dae Won Jun, Kiseok Jang, Byung Hoon Lee, Kye Jung Shin
Background/Aims: Intestinal cholesterol absorption includes intestinal Niemann-Pick C1-like 1 (NPC1L1) and is an important target pathway in nonalcoholic fatty liver disease (NAFLD). We investigated the expression of NPC1L1 and its correlation with liver X receptor (LXR) expression in peripheral mononuclear (PMN) cells in patients with NAFLD. Methods: We evaluated intestinal expression of NPC1L1 in 25 NAFLD patients and 28 healthy controls. We calculated the mRNA expression levels of LXR and farnesoid X receptor (FXR), which are master players of cholesterol metabolism in PMN cells...
February 23, 2018: Korean Journal of Internal Medicine
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