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https://www.readbyqxmd.com/read/29778664/gestational-diabetes-mellitus-modulates-cholesterol-homeostasis-in-human-fetoplacental-endothelium
#1
Yidan Sun, Susanne Kopp, Jasmin Strutz, Chaitanya Chakravarthi Gali, Martina Zandl-Lang, Elham Fanaee-Danesh, Andrijana Kirsch, Silvija Cvitic, Saša Frank, Richard Saffery, Ingemar Björkhem, Gernot Desoye, Christian Wadsack, Ute Panzenboeck
Gestational diabetes mellitus (GDM) is associated with excessive oxidative stress which may affect placental vascular function. Cholesterol homeostasis is crucial for maintaining fetoplacental endothelial function. We aimed to investigate whether and how GDM affects cholesterol metabolism in human fetoplacental endothelial cells (HPEC). HPEC were isolated from fetal term placental arterial vessels of GDM or control subjects. Cellular reactive oxygen species (ROS) were detected by H2 DCFDA fluorescent dye. Oxysterols were quantified by gas chromatography-mass spectrometry analysis...
May 17, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29774529/inhibition-of-prmt3-activity-selectively-impairs-lxr-driven-transcription-of-hepatic-lipogenic-genes-in-vivo
#2
Joya E Nahon, Christianne Groeneveldt, Janine J Geerling, Miranda Van Eck, Menno Hoekstra
BACKGROUND AND PURPOSE: Agonists for the liver X receptor (LXR) are considered promising therapeutic moieties in cholesterol-driven diseases by promoting cellular cholesterol efflux pathways. However, current clinical application of these agents is hampered by the concomitant LXR-induced activation of a lipogenic transcriptional network, leading to hepatic steatosis. Recent studies have suggested that protein arginine methyltransferase 3 (PRMT3) may act as a selective co-activator of LXR activity...
May 18, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29769320/o-glcnac-transferase-missense-mutations-linked-to-x-linked-intellectual-disability-deregulate-genes-involved-in-cell-fate-determination-and-signaling
#3
Nithya Selvan, Stephan George, Fatema J Serajee, Marie Shaw, Lynne Hobson, Vera M Kalscheuer, Nripesh Prasad, Shawn E Levy, Juliet Taylor, Salim Afitmos, Charles E Schwartz, Ahm M Huq, Jozef Gecz, Lance Wells
It is estimated that ~1% of the world's population has intellectual disability, with males affected more often than females. OGT is an X-linked gene encoding for the enzyme O-GlcNAc transferase (OGT), which carries out the reversible addition of N-Acetylglucosamine (GlcNAc) to Ser/Thr residues of its intracellular substrates. Three missense mutations in the tetratricopeptide (TPR) repeats of OGT have recently been reported to cause X-linked Intellectual Disability (XLID). Here we report the discovery of two additional novel missense mutations (c...
May 16, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29760600/comprehensive-proteome-analysis-of-nasal-lavage-samples-after-controlled-exposure-to-welding-nanoparticles-shows-an-induced-acute-phase-and-a-nuclear-receptor-lxr-rxr-activation-that-influence-the-status-of-the-extracellular-matrix
#4
Neserin Ali, Stefan Ljunggren, Helen M Karlsson, Aneta Wierzbicka, Joakim Pagels, Christina Isaxon, Anders Gudmundsson, Jenny Rissler, Jörn Nielsen, Christian H Lindh, Monica Kåredal
Background: Epidemiological studies have shown that many welders experience respiratory symptoms. During the welding process a large number of airborne nanosized particles are generated, which might be inhaled and deposited in the respiratory tract. Knowledge of the underlying mechanisms behind observed symptoms is still partly lacking, although inflammation is suggested to play a central role. The aim of this study was to investigate the effects of welding fume particle exposure on the proteome expression level in welders suffering from respiratory symptoms, and changes in protein mediators in nasal lavage samples were analyzed...
2018: Clinical Proteomics
https://www.readbyqxmd.com/read/29746821/lansoprazole-reduces-renal-cyst-in-polycystic-kidney-disease-via-inhibition-of-cell-proliferation-and-fluid-secretion
#5
Jiriporn Nantavishit, Varanuj Chatsudthipong, Sunhapas Soodvilai
Renal cyst development and expansion in autosomal dominant polycystic kidney disease (ADPKD) is mediated by abnormal cyst-ling cell proliferation and fluid accumulation. Liver X receptor (LXR)-activating ligands suppresses renal cyst enlargement by modulation of cysticfibrosis transmembrane conductance regulator (CFTR)-mediated fluid accumulation. Lansoprazole has been reported as agonist of LXR, and shows an anti-proliferative effect in cancer cells. Here, lansoprazole's pharmacological effect and underlying mechanism on renal cyst development and expansion in in vitro; human ADPKD cyst-lining epithelial cell line and Type I Mardin Darby Canine Kidney (MDCK) cells, and in vivo models was investigated...
May 7, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29743930/lxr%C3%A9-participates-in-the-mtor-s6k1-srebp-1c-signaling-pathway-during-sodium-palmitate-induced-lipogenesis-in-hepg2-cells
#6
Youping Zhou, Shengjie Yu, Can Cai, Li Zhong, Huihong Yu, Wei Shen
Background: The aim of this study was to investigate how the signaling pathway downstream of mTOR/S6K1 contributes to the regulation of SREBP-1c expression during lipogenesis in HepG2 cells. Methods: The model of steatosis was established using human hepatocytes HepG2 and inducting them with sodium palmitate. mTOR, S6K1 and LXRα were inhibited by rapamycin, PF-4708671 and siRNA-LXRα, respectively. After a variety of different treatment, the levels of intracellular triglycerides, the accumulation of lipid droplets and the expression levels of related genes were detected...
2018: Nutrition & Metabolism
https://www.readbyqxmd.com/read/29743292/cholesterol-negatively-regulates-il-9-producing-cd8-t-cell-differentiation-and-antitumor-activity
#7
Xingzhe Ma, Enguang Bi, Chunjian Huang, Yong Lu, Gang Xue, Xing Guo, Aibo Wang, Maojie Yang, Jianfei Qian, Chen Dong, Qing Yi
CD8+ T cells can be polarized into IL-9-secreting (Tc9) cells. We previously showed that adoptive therapy using tumor-specific Tc9 cells generated stronger antitumor responses in mouse melanoma than classical Tc1 cells. To understand why Tc9 cells exert stronger antitumor responses, we used gene profiling to compare Tc9 and Tc1 cells. Tc9 cells expressed different levels of cholesterol synthesis and efflux genes and possessed significantly lower cholesterol content than Tc1 cells. Unique to Tc9, but not other CD8+ or CD4+ T cell subsets, manipulating cholesterol content in polarizing Tc9 cells significantly affected IL-9 expression and Tc9 differentiation and antitumor response in vivo...
May 9, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29741759/anionic-nanoliposomes-reduced-atherosclerosis-progression-in-low-density-lipoprotein-receptor-ldlr-deficient-mice-fed-a-high-fat-diet
#8
Smriti M Krishna, Joseph V Moxon, Roby J Jose, Jiaze Li, Amirhossein Sahebkar, Mahmoud R Jaafari, Mahdi Hatamipour, Dawie Liu, Jonathan Golledge
Atherosclerosis is a systemic disease characterized by the deposition of cholesterol and inflammatory cells within the arterial wall. Removal of cholesterol from the vessel wall may have an impact on the size and composition of atherosclerotic lesions. Anionic phospholipids or liposome vesicles composed of a lipid bilayer such as nanoliposomes have been suggested as treatments for dyslipidemia. In this study, we investigated the effect of anionic nanoliposomes on atherosclerosis in a mouse model. Low-density lipoprotein receptor knockout mice (Ldlr-/- ) were fed with an atherosclerosis promoting high fat and cholesterol (HFC) diet for 12 weeks...
May 9, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29739800/loss-of-the-liver-x-receptors-disrupts-the-balance-of-hematopoietic-populations-with-detrimental-effects-on-endothelial-progenitor-cells
#9
Adil Rasheed, Ricky Tsai, Carolyn L Cummins
BACKGROUND: The liver X receptors (LXRs; α/β) are nuclear receptors known to regulate cholesterol homeostasis and the production of select hematopoietic populations. The objective of this study was to determine the importance of LXRs and a high-fat high-cholesterol diet on global hematopoiesis, with special emphasis on endothelial progenitor cells (EPCs), a vasoreparative cell type that is derived from bone marrow hematopoietic stem cells. METHODS AND RESULTS: Wild-type and LXR double-knockout ( Lxr αβ -/- ) mice were fed a Western diet (WD) to increase plasma cholesterol levels...
May 8, 2018: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29738435/crebh-regulates-systemic-glucose-and-lipid-metabolism
#10
REVIEW
Yoshimi Nakagawa, Hitoshi Shimano
The cyclic adenosine monophosphate (cAMP)-responsive element-binding protein H (CREBH, encoded by CREB3L3) is a membrane-bound transcriptional factor that primarily localizes in the liver and small intestine. CREBH governs triglyceride metabolism in the liver, which mediates the changes in gene expression governing fatty acid oxidation, ketogenesis, and apolipoproteins related to lipoprotein lipase (LPL) activation. CREBH in the small intestine reduces cholesterol transporter gene Npc1l1 and suppresses cholesterol absorption from diet...
May 8, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29733910/the-contribution-of-cholesterol-and-epigenetic-changes-to-the-pathophysiology-of-breast-cancer
#11
REVIEW
Maliha T Munir, Christopher Ponce, Catherine A Powell, Kaiser Tarafdar, Teru Yanagita, Mahua Choudhury, Lauren S Gollahon, Shaikh M Rahman
Breast cancer is one of the most commonly diagnosed cancers in women. Accumulating evidence suggests that cholesterol plays an important role in the development of breast cancer. Even though the mechanistic link between these two factors is not well understood, one possibility is that dysregulated cholesterol metabolism may affect lipid raft and membrane fluidity and can promote tumor development. Current studies have shown oxysterol 27-hydroxycholesterol (27-HC) as a critical regulator of cholesterol and breast cancer pathogenesis...
May 4, 2018: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/29731879/lxr-ligands-induce-apoptosis-of-egfr-tki-resistant-human-lung-cancer-cells-in-vitro-by-inhibiting-akt-nf-%C3%AE%C2%BAb-activation
#12
Siwen Liu, Haixia Cao, Dan Chen, Shaorong Yu, Huanhuan Sha, Jianzhong Wu, Rong Ma, Zhuo Wang, Changwen Jing, Junying Zhang, Jifeng Feng
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are efficient in treating patients with non-small cell lung cancer (NSCLC) harboring EGFR activating mutations. Unfortunately, nearly all patients ultimately acquire resistance to EGFR-TKI treatment. Liver X receptors (LXRs) can regulate tumor growth in various cancer cell lines. The present study indicated that LXR agonist combined with gefitinib weakened Akt-nuclear factor (NF)-κB activation and inhibited the expression levels of apoptosis-related proteins in vitro ...
May 2018: Oncology Letters
https://www.readbyqxmd.com/read/29728575/dual-extraction-of-mrna-and-lipids-from-a-single-biological-sample
#13
Normand Podechard, Simon Ducheix, Arnaud Polizzi, Frédéric Lasserre, Alexandra Montagner, Vincent Legagneux, Edwin Fouché, Fabrice Saez, Jean-Marc Lobaccaro, Laila Lakhal, Sandrine Ellero-Simatos, Pascal G Martin, Nicolas Loiseau, Justine Bertrand-Michel, Hervé Guillou
The extraction of RNA and lipids from a large number of biological samples is time-consuming and costly with steps required for both transcriptomic and lipidomic approaches. Most protocols rely on independent extraction of nucleic acids and lipids from a single sample, thereby increasing the need for biological material and inducing variability in data analysis. We investigated whether it is possible to use a standard RNA extraction procedure to analyze not only RNA levels, but also lipids in a single liver sample...
May 4, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29712848/rational-application-of-macrophage-specific-lxr-agonists-avoids-the-pitfalls-of-srebp-induced-lipogenesis
#14
Jason A Magida, Ronald M Evans
No abstract text is available yet for this article.
April 30, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29706895/-liversex-computational-model-sexual-aspects-in-hepatic-metabolism-and-abnormalities
#15
Tanja Cvitanović Tomaš, Žiga Urlep, Miha Moškon, Miha Mraz, Damjana Rozman
The liver is to date the best example of a sexually dimorphic non-reproductive organ. Over 1,000 genes are differentially expressed between sexes indicating that female and male livers are two metabolically distinct organs. The spectrum of liver diseases is broad and is usually prevalent in one or the other sex, with different contributing genetic and environmental factors. It is thus difficult to predict individual's disease outcomes and treatment options. Systems approaches including mathematical modeling can aid importantly in understanding the multifactorial liver disease etiology leading toward tailored diagnostics, prognostics and therapy...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29695588/mindin-deficiency-in-macrophages-protects-against-foam-cell-formation-and-atherosclerosis-by-targeting-lxr-%C3%AE
#16
Cheng Zhang, Juan-Juan Qin, Fu-Han Gong, Jing-Jing Tong, Wen-Lin Cheng, Haiping Wang, Yan Zhang, Xueyong Zhu, Zhi-Gang She, Hao Xia, Li-Hua Zhu
Abstract Background - Mindin, which is a highly conserved ECM protein, has been documented to play pivotal roles in regulating angiogenesis, inflammatory processes and immune responses. The aim of this study was to assess whether mindin contributes to the development of atherosclerosis. Methods and Results - A significant upregulation of Mindin expression was observed in the serum, arteries and atheromatous plaques of ApoE-/-  mice after HFD treatment. Mindin-/- ApoE-/- mice and macrophage-specific mindin overexpression in ApoE-/- mice (Lyz2-mindin-TG) were generated to evaluate the effect of mindin on the development of atherosclerosis...
April 25, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29691317/cholesterol-signaling-in-single-cells-lessons-from-star-and-sm-fish
#17
REVIEW
Colin R Jefcoate, Jinwoo Lee
Cholesterol is an important regulator of cell signaling, both through direct impacts on cell membranes and through oxy-metabolites that activate specific receptors (steroids, hydroxy-cholesterols, bile acids). Cholesterol moves slowly through and between cell membranes with the assistance of specific binding proteins and transfer processes. The prototype cholesterol regulator is the Steroidogenesis Acute Regulatory (STAR), which moves cholesterol into mitochondria, where steroid synthesis is initiated by cytochrome P450 11A1 in multiple endocrine cell types...
May 2018: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/29690611/the-role-of-ppar-and-its-cross-talk-with-car-and-lxr-in-obesity-and-atherosclerosis
#18
REVIEW
Pengfei Xu, Yonggong Zhai, Jing Wang
The prevalence of obesity and atherosclerosis has substantially increased worldwide over the past several decades. Peroxisome proliferator-activated receptors (PPARs), as fatty acids sensors, have been therapeutic targets in several human lipid metabolic diseases, such as obesity, atherosclerosis, diabetes, hyperlipidaemia, and non-alcoholic fatty liver disease. Constitutive androstane receptor (CAR) and liver X receptors (LXRs) were also reported as potential therapeutic targets for the treatment of obesity and atherosclerosis, respectively...
April 23, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29681863/tangshen-formula-attenuates-diabetic-nephropathy-by-promoting-abca1-mediated-renal-cholesterol-efflux-in-db-db-mice
#19
Peng Liu, Liang Peng, Haojun Zhang, Patrick Ming-Kuen Tang, Tingting Zhao, Meihua Yan, Hailing Zhao, Xiaoru Huang, Huiyao Lan, Ping Li
The commonly prescribed Tangshen Formula (TSF) is a traditional Chinese formulation that has been shown to reduce plasma lipid metabolism and proteinuria and improve the estimated glomerular filtration rate (eGFR) in patients with diabetic kidney disease. This study investigated the underlying mechanism whereby TSF regulates renal lipid accumulation and ameliorates diabetic renal injuries in spontaneous diabetic db/db mice and in vitro in sodium palmitate (PA)-stimulated and Abca1-SiRNA-transfected mouse tubular epithelial cells (mTECs)...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29670908/liver-x-receptor-inverse-agonist-sr9243-suppresses-nonalcoholic-steatohepatitis-intrahepatic-inflammation-and-fibrosis
#20
Peng Huang, Benson Kaluba, Xiao-Lin Jiang, Shi Chang, Xiao-Feng Tang, Lin-Feng Mao, Zhi-Peng Zhang, Fei-Zhou Huang
Abnormal metabolism of cholesterol may be a contributing factor in nonalcoholic steatohepatitis (NASH) pathogenesis. Accumulating evidence has shown that liver X receptor (LXR) is closely related to intrahepatic inflammation and fibrosis. In this study, we evaluated the effects of a novel liver-specific LXR inverse agonist, SR9243, on antifibrosis in NASH mice. A high-cholesterol diet was employed to induce NASH in BALB/c mice by either carbon tetrachloride (CCL4) administration or bile-duct ligation (BDL)...
2018: BioMed Research International
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