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https://www.readbyqxmd.com/read/28315462/implications-of-cerebrovascular-atp-binding-cassette-transporter-g1-abcg1-and-apolipoprotein-m-in-cholesterol-transport-at-the-blood-brain-barrier
#1
Alexandra Carmen Kober, Anil Paul Chirackal Manavalan, Carmen Tam-Amersdorfer, Andreas Holmér, Ahmed Saeed, Elham Fanaee Danesh, Martina Zandl, Nicole Maria Albrecher, Ingemar Björkhem, Gerhard M Kostner, Björn Dahlbäck, Ute Panzenboeck
Impaired cholesterol/lipoprotein metabolism is linked to neurodegenerative diseases such as Alzheimer's disease (AD). Cerebral cholesterol homeostasis is maintained by the highly efficient blood-brain barrier (BBB) and flux of the oxysterols 24(S)-hydroxycholesterol and 27-hydroxycholesterol, potent liver-X-receptor (LXR) activators. HDL and their apolipoproteins are crucial for cerebral lipid transfer, and loss of ATP binding cassette transporters (ABC)G1 and G4 results in toxic accumulation of oxysterols in the brain...
March 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28315324/nucleolin-protects-macrophages-from-oxldl-induced-foam-cell-formation-through-up-regulating-abca1-expression
#2
Yuanbin Li, Bimei Jiang, Pengfei Liang, Zhongyi Tong, Meidong Liu, Qinglan Lv, Yanjuan Liu, Xuanyou Liu, Yuting Tang, Xianzhong Xiao
Our recent studies have indicated that nucleolin, as a multifunctional RNA-binding protein, exerts protective effects in the myocardial cells and endothelial cells under the condition of oxidative stress. However, the function of nucleolin and its potential mechanism in macrophage-derived foam cell formation remain largely unexplored. ApoE-/- mice were fed with a high-fat diet (HFD) for 10-24 weeks. Protein expression was measured by western blotting or immunofluorescence, and gene expression at the mRNA level was detected by qRT-PCR...
March 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28301372/news-on-the-molecular-regulation-and-function-of-hepatic-low-density-lipoprotein-receptor-and-ldlr-related-protein-1
#3
Bart van de Sluis, Melinde Wijers, Joachim Herz
PURPOSE OF REVIEW: Clearing of atherogenic lipoprotein particles by the liver requires hepatic low-density lipoprotein receptor (LDLR) and LDLR-related protein 1 (LRP1). This review highlights recent studies that have expanded our understanding of the molecular regulation and metabolic functions of LDLR and LRP1 in the liver. RECENT FINDINGS: Various proteins orchestrate the intracellular trafficking of LDLR and LRP1. After internalization, the receptors are redirected via recycling endosomes to the cell surface...
March 15, 2017: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/28296196/sirt6-reduces-macrophage-foam-cell-formation-by-inducing-autophagy-and-cholesterol-efflux-under-ox-ldl-condition
#4
Jiangping He, Guangya Zhang, Qi Pang, Cong Yu, Jie Xiong, Jing Zhu, Fengling Chen
SIRT6 is a pivotal regulator of lipid metabolism. It is also closely connected to cardiovascular diseases, which are the main cause of death in diabetic patients. We observed a decrease in the expression of SIRT6 and key autophagy effectors (ATG5, LC3B, and LAMP1) in ox-LDL-induced foam cells, a special form of lipid-laden macrophages. In these cells, SIRT6 WT but not SIRT6 H133Y overexpression markedly reduced foam cell formation, as shown by Oil Red O staining, while inducing autophagy flux, as determined by both mRFP-GFP-LC3 labeling and transmission electron microscopy...
March 9, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28293855/growth-hormone-receptor-knockdown-sensitizes-human-melanoma-cells-to-chemotherapy-by-attenuating-expression-of-abc-drug-efflux-pumps
#5
Reetobrata Basu, Nicholas Baumgaertel, Shiyong Wu, John J Kopchick
Melanoma remains one of the most therapy-resistant forms of human cancer despite recent introductions of highly efficacious targeted therapies. The intrinsic therapy resistance of human melanoma is largely due to abundant expression of a repertoire of xenobiotic efflux pumps of the ATP-binding cassette (ABC) transporter family. Here, we report that GH action is a key mediator of chemotherapeutic resistance in human melanoma cells. We investigated multiple ABC efflux pumps (ABCB1, ABCB5, ABCB8, ABCC1, ABCC2, ABCG1, and ABCG2) reportedly associated with melanoma drug resistance in different human melanoma cells and tested the efficacy of five different anti-cancer compounds (cisplatin, doxorubicin, oridonin, paclitaxel, vemurafenib) with decreased GH action...
March 14, 2017: Hormones & Cancer
https://www.readbyqxmd.com/read/28273782/active-liver-x-receptor-signaling-in-phagocytes-in-multiple-sclerosis-lesions
#6
Jo Mailleux, Tim Vanmierlo, Jeroen Fj Bogie, Elien Wouters, Dieter Lütjohann, Jerome Ja Hendriks, Jack van Horssen
OBJECTIVE: We sought to determine the liver X receptor (LXR) ligands present in human macrophages after myelin phagocytosis and whether LXRs are activated in multiple sclerosis (MS) lesions. METHODS: We used real-time quantitative polymerase chain reaction (PCR) and immunohistochemistry to determine expression of LXRs and their response genes in human phagocytes after myelin phagocytosis and in active MS lesions. We used gas chromatographic/mass spectrometric analysis to determine LXR-activating oxysterols and cholesterol precursors present and formed in myelin and myelin-incubated cells, respectively...
February 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28264879/abcg1-regulates-pulmonary-surfactant-metabolism-in-mice-and-men
#7
Thomas Q de Aguiar Vallim, Elinor Lee, David J Merriott, Christopher N Goulbourne, Joan Cheng, Angela Cheng, Ayelet Gonen, Ryan M Allen, Elisa N D Palladino, David A Ford, Tisha Wang, Ángel Baldán, Elizabeth J Tarling
Idiopathic pulmonary alveolar proteinosis (PAP) is a rare lung disease characterized by accumulation of surfactant. Surfactant synthesis and secretion are restricted to epithelial type 2 pneumocytes (T2 cells). Clearance of surfactant is dependent upon T2 cells and macrophages. ATP Binding Cassette Transporter G1 (ABCG1) is highly expressed in both T2 cells and macrophages. ABCG1-deficient mice accumulate surfactant, lamellar body-loaded T2 cells, lipid-loaded macrophages, B-1 lymphocytes and immunoglobulins, clearly demonstrating ABCG1 has a critical role in pulmonary homeostasis...
March 6, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28264842/contributions-of-both-atp-binding-cassette-transporter-and-cyp51a-proteins-are-essential-for-azole-resistance-in-aspergillus-fumigatus
#8
Sanjoy Paul, Daniel Diekema, W Scott Moye-Rowley
While azole drugs targeting the biosynthesis of ergosterol are effective antifungal agents, their extensive use has led to the development of resistant organisms. Infections involving azole resistant forms of the filamentous fungus Aspergillus fumigatus are often associated with genetic changes in the cyp51A gene encoding the lanosterol α14 demethylase target enzyme. Both a sequence duplication in the cyp51A promoter (TR34) as well as a substitution mutation in the coding sequence (L98H) are required for full expression of azole resistance...
March 6, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28241820/examining-the-role-of-abc-lipid-transporters-in-pulmonary-lipid-homeostasis-and-inflammation
#9
REVIEW
Amanda B Chai, Alaina J Ammit, Ingrid C Gelissen
Respiratory diseases including asthma and chronic obstructive pulmonary disease (COPD) are characterised by excessive and persistent inflammation. Current treatments are often inadequate for symptom and disease control, and hence new therapies are warranted. Recent emerging research has implicated dyslipidaemia in pulmonary inflammation. Three ATP-binding cassette (ABC) transporters are found in the mammalian lung - ABCA1, ABCG1 and ABCA3 - that are involved in movement of cholesterol and phospholipids from lung cells...
February 28, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28241068/liver-x-receptor-agonist-treatment-significantly-affects-phenotype-and-transcriptome-of-apoe3-and-apoe4-abca1-haplo-deficient-mice
#10
Alexis Y Carter, Florent Letronne, Nicholas F Fitz, Anais Mounier, Cody M Wolfe, Kyong Nyon Nam, Valerie L Reeves, Hafsa Kamboh, Iliya Lefterov, Radosveta Koldamova
ATP-binding cassette transporter A1 (ABCA1) controls cholesterol and phospholipid efflux to lipid-poor apolipoprotein E (APOE) and is transcriptionally controlled by Liver X receptors (LXRs) and Retinoic X Receptors (RXRs). In APP transgenic mice, lack of Abca1 increased Aβ deposition and cognitive deficits. Abca1 haplo-deficiency in mice expressing human APOE isoforms, increased level of Aβ oligomers and worsened memory deficits, preferentially in APOE4 mice. In contrast upregulation of Abca1 by LXR/RXR agonists significantly ameliorated pathological phenotype of those mice...
2017: PloS One
https://www.readbyqxmd.com/read/28213390/epigenetic-patterns-in-blood-associated-with-lipid-traits-predict-incident-coronary-heart-disease-events-and-are-enriched-for-results-from-genome-wide-association-studies
#11
Åsa K Hedman, Michael M Mendelson, Riccardo E Marioni, Stefan Gustafsson, Roby Joehanes, Marguerite R Irvin, Degui Zhi, Johanna K Sandling, Chen Yao, Chunyu Liu, Liming Liang, Tianxiao Huan, Allan F McRae, Serkalem Demissie, Sonia Shah, John M Starr, L Adrienne Cupples, Panos Deloukas, Timothy D Spector, Johan Sundström, Ronald M Krauss, Donna K Arnett, Ian J Deary, Lars Lind, Daniel Levy, Erik Ingelsson
BACKGROUND: Genome-wide association studies have identified loci influencing circulating lipid concentrations in humans; further information on novel contributing genes, pathways, and biology may be gained through studies of epigenetic modifications. METHODS AND RESULTS: To identify epigenetic changes associated with lipid concentrations, we assayed genome-wide DNA methylation at cytosine-guanine dinucleotides (CpGs) in whole blood from 2306 individuals from 2 population-based cohorts, with replication of findings in 2025 additional individuals...
January 2017: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/28205181/abc-transporter-mediated-sterol-export-from-cells-using-radiolabeled-sterols
#12
Alryel Yang, Ingrid C Gelissen
Cholesterol export from cells to extracellular acceptors represents the first step of the reverse cholesterol transport process and is an essential part of the multifaceted pathway for cells to control their cholesterol levels. Malfunction of this pathway leads to cholesterol accumulation in cells such as macrophages, which can form the basis of conditions like atherosclerosis. A number of ATP-binding cassette (ABC) transporters, namely ABCA1, ABCA7, ABCG1, and ABCG4, play an essential role in this process...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28194238/epigenome-wide-association-study-ewas-on-lipids-the-rotterdam-study
#13
Kim V E Braun, Klodian Dhana, Paul S de Vries, Trudy Voortman, Joyce B J van Meurs, Andre G Uitterlinden, Albert Hofman, Frank B Hu, Oscar H Franco, Abbas Dehghan
BACKGROUND: DNA methylation is a key epigenetic mechanism that is suggested to be associated with blood lipid levels. We aimed to identify CpG sites at which DNA methylation levels are associated with blood levels of triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and total cholesterol in 725 participants of the Rotterdam Study, a population-based cohort study. Subsequently, we sought replication in a non-overlapping set of 760 participants...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28165022/the-atp-binding-cassette-transporter-abcg1-localizes-to-cortical-actin-filaments
#14
Elvis Pandzic, Ingrid C Gelissen, Renee Whan, Philip J Barter, Dmitri Sviridov, Katharina Gaus, Kerry-Anne Rye, Blake J Cochran
The ATP-binding cassette sub-family G member 1 (ABCG1) exports cellular cholesterol to high-density lipoproteins (HDL). However, a number of recent studies have suggested ABCG1 is predominantly localised to intracellular membranes. In this study, we found that ABCG1 was organized into two distinct cellular pools: one at the plasma membrane and the other associated with the endoplasmic reticulum (ER). The plasma membrane fraction was organized into filamentous structures that were associated with cortical actin filaments...
February 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/27996196/reverse-translational-study-of-fenofibrate-s-observed-effects-in-diabetes-associated-retinopathy
#15
R A Farris, E T Price
Clinical trials suggest that fenofibrate reduces the progression of retinopathies in patients with type 2 diabetes. Furthermore, patients with retinopathies have elevated levels of inflammatory chemokines and dysfunctional retinal angiogenesis. Therefore, we investigated the effects of fenofibrate on the production of inflammatory chemokines and genes associated with angiogenesis. Retinal pigment epithelial cells (RPECs) were cultured with IL-1β and fenofibrate ranging from 1-50 μM. ENA-78, IL-8, and RANTES were measured in cell culture by ELISA...
March 2017: Clinical and Translational Science
https://www.readbyqxmd.com/read/27995417/high-density-lipoprotein-from-subjects-with-coronary-artery-disease-promotes-macrophage-foam-cell-formation-role-of-scavenger-receptor-cd36-and-erk-mapk-signaling
#16
S Sini, D Deepa, S Harikrishnan, N Jayakumari
Although high-density lipoprotein is atheroprotective, it can become dysfunctional in chronic inflammatory conditions and increase cardiovascular risk. We previously demonstrated that HDL from subjects with documented coronary artery disease is dysfunctional and is pro-oxidant/proinflammatory in macrophages. Here we examined the influence of dysfunctional/proinflammatory HDL (piHDL) on lipid accumulation in human macrophages, in comparison to functional HDL (nHDL). Exposure of macrophages to piHDL, in contrast to nHDL, resulted in oxidative stress and marked uptake of lipids from piHDL, leading to the formation of foam cell phenotype as noted by oil red O staining with concomitant increase in total cellular cholesterol content...
March 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/27994765/discovery-of-highly-potent-liver-x-receptor-%C3%AE-agonists
#17
Ellen K Kick, Brett B Busch, Richard Martin, William C Stevens, Venkataiah Bollu, Yinong Xie, Brant C Boren, Michael C Nyman, Max H Nanao, Lam Nguyen, Artur Plonowski, Ira G Schulman, Grace Yan, Huiping Zhang, Xiaoping Hou, Meriah N Valente, Rangaraj Narayanan, Kamelia Behnia, A David Rodrigues, Barry Brock, James Smalley, Glenn H Cantor, John Lupisella, Paul Sleph, Denise Grimm, Jacek Ostrowski, Ruth R Wexler, Todd Kirchgessner, Raju Mohan
Introducing a uniquely substituted phenyl sulfone into a series of biphenyl imidazole liver X receptor (LXR) agonists afforded a dramatic potency improvement for induction of ATP binding cassette transporters, ABCA1 and ABCG1, in human whole blood. The agonist series demonstrated robust LXRβ activity (>70%) with low partial LXRα agonist activity (<25%) in cell assays, providing a window between desired blood cell ABCG1 gene induction in cynomolgus monkeys and modest elevation of plasma triglycerides for agonist 15...
December 8, 2016: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27989886/intracoronary-imaging-cholesterol-efflux-and-transcriptomes-after-intensive%C3%A2-statin%C3%A2-treatment-the-yellow-ii-study
#18
Annapoorna S Kini, Yuliya Vengrenyuk, Khader Shameer, Akiko Maehara, Meerarani Purushothaman, Takahiro Yoshimura, Mitsuaki Matsumura, Melissa Aquino, Nezam Haider, Kipp W Johnson, Ben Readhead, Brian A Kidd, Jonathan E Feig, Prakash Krishnan, Joseph Sweeny, Mahajan Milind, Pedro Moreno, Roxana Mehran, Jason C Kovacic, Usman Baber, Joel T Dudley, Jagat Narula, Samin Sharma
BACKGROUND: Despite extensive evidence demonstrating the beneficial effects of statins on clinical outcomes, the mechanisms underlying these effects remain elusive. OBJECTIVES: This study assessed changes in plaque morphology using intravascular imaging, with a comprehensive evaluation of cholesterol efflux capacity (CEC) and peripheral blood mononuclear cell (PBMC) transcriptomics in patients receiving high-dose statin therapy. METHODS: In a prospective study, 85 patients with stable coronary artery disease underwent percutaneous coronary intervention for a culprit lesion, followed by intracoronary multimodality imaging, including optical coherence tomography (OCT) of an obstructive nonculprit lesion...
February 14, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/27980243/analysis-of-serum-cholesterol-efflux-capacity-in-a-minipig-model-of-nonischemic-heart-failure
#19
Federico Bigazzi, Maria Pia Adorni, Mariarita Puntoni, Francesco Sbrana, Vincenzo Lionetti, Beatrice Dal Pino, Elda Favari, Fabio A Recchia, Franco Bernini, Tiziana Sampietro
AIM: Circulating levels of high-density lipoprotein cholesterol (HDL-C) are decreased in patients with heart failure (HF). We tested whether HDL-C serum levels are associated with cardiac contractile dysfunction in a minipig HF model. METHODS: Blood samples were collected from 13 adult male minipigs: 1) before pacemaker implantation, 2) 10 days after surgery, and 3) 3 weeks after high-rate LV pacing. Serum cholesterol efflux capacity (CEC), an index of HDL functionality, was assessed through four mechanisms: ATP Binding Cassette transporter A1 (ABCA1), ATP Binding Cassette transporter G1 (ABCG1), Scavenger Receptor-Class B Type I (SR-BI) and Passive Diffusion (PD)...
December 15, 2016: Journal of Atherosclerosis and Thrombosis
https://www.readbyqxmd.com/read/27968834/methylation-loci-associated-with-body-mass-index-waist-circumference-and-waist-to-hip-ratio-in-chinese-adults-an-epigenome-wide-analysis
#20
Biqi Wang, Wenjing Gao, Jun Li, Canqing Yu, Weihua Cao, Jun Lv, Zengchang Pang, Liming Cong, Hua Wang, Xianping Wu, Liming Liang, Tangchun Wu, Liming Li
BACKGROUND: DNA methylation has been implicated in the pathology of obesity, but little is known about such epigenetic variants in Chinese people. We conducted an epigenome-wide analysis of methylation at CpG sites in relation to body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR) among Chinese adult populations. METHODS: 469 twins from the Chinese National Twin Registry were the discovery cohort. After quality control, methylation levels in whole blood leukocyte DNA were tested for association with BMI, WC, and WHR using mixed linear regressions, adjusting for demographics, lifestyle, and family structure...
October 2016: Lancet
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