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https://www.readbyqxmd.com/read/29144234/lrp1-integrates-murine-macrophage-cholesterol-homeostasis-and-inflammatory-responses-in-atherosclerosis
#1
Xunde Xian, Yinyuan Ding, Marco Dieckmann, Li Zhou, Florian Plattner, Mingxia Liu, John S Parks, Robert E Hammer, Philippe Boucher, Shirling Tsai, Joachim Herz
Low-density lipoprotein receptor-related protein 1 (LRP1) is a multifunctional cell surface receptor with diverse physiological roles, ranging from cellular uptake of lipoproteins and other cargo by endocytosis to sensor of the extracellular environment and integrator of a wide range of signaling mechanisms. As a chylomicron remnant receptor, LRP1 controls systemic lipid metabolism in concert with the LDL receptor in the liver, whereas in smooth muscle cells (SMC) LRP1 functions as a co-receptor for TGFβ and PDGFRβ in reverse cholesterol transport and the maintenance of vascular wall integrity...
November 16, 2017: ELife
https://www.readbyqxmd.com/read/29133384/estrogen-and-high-fat-diet-induced-alterations-in-c57bl-6-mice-endometrial-transcriptome-profile
#2
Yali Cheng, Qiaoying Lv, Bingying Xie, Bingyi Yang, Weiwei Shan, Chengcheng Ning, Bing Li, Liying Xie, Chao Gu, Xuezhen Luo, Xiaojun Chen, Qin Zhu
Unopposed estrogen stimulation and insulin resistance are known to play important roles in endometrial cancer (EC), but the interaction between these two factors and how they contribute to endometrial lesions are not completely elucidated. To investigate the endometrial transcriptome profile and the associated molecular pathway alterations, we established an ovariectomized C57BL/6 mouse model treated with subcutaneous implantation of 17-β estradiol (E2) pellet and/or high-fat diet (HFD) for 12 weeks to mimic sustained estrogen stimulation and insulin resistance...
November 13, 2017: Endocrine Connections
https://www.readbyqxmd.com/read/29130021/transgenic-overexpression-of-steroid-sulfatase-alleviates-cholestasis
#3
Mengxi Jiang, Meishu Xu, Songrong Ren, Kyle W Selcer, Wen Xie
Background and Aim: Sulfotransferase (SULT)-mediated sulfation and steroid sulfatase (STS)-mediated desulfation represent two critical mechanisms that regulate the chemical and functional homeostasis of endogenous and exogenous molecules. STS catalyzes the hydrolysis of steroid sulfates to form hydroxysteroids. Oxygenated cholesterol derivative oxysterols are known to be endogenous ligands of the liver X receptor (LXR), a nuclear receptor with anti-cholestasis activity, whereas the sulfated oxysterols antagonize LXR signaling...
June 2017: Liver Res
https://www.readbyqxmd.com/read/29128625/lxr-activation-increases-the-expression-of-gnrh-and-%C3%AE-msh-in-the-rat-hypothalamus-in-vivo
#4
María Sol Kruse, Lucas Gabriel Suarez, Héctor Coirini
Liver X receptors (LXR) are important transcription factors involved in the regulation of carbohydrate and lipid metabolism. Recently, we described LXR receptors expression in the hypothalamus but their function in this brain area remains unknown. Here, we evaluated the function of LXR on the expression of factors produced in the hypothalamus in vitro and in vivo by Western blotting and immunocytochemistry. More precisely we studied the expression of GnRH and GHRH, αMSH and NPY in male Sprague-Dawley rats...
November 9, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/29127736/liver-x-receptor-activation-inhibits-sglt2-mediated-glucose-transport-in-human-renal-proximal-tubular-cells
#5
Pattira Chonlaket, Teerasak Wongwan, Sunhapas Soodvilai
Liver X receptors (LXRs) are members of a nuclear receptor family consisting of two isoforms, LXR-α and LXR-β. They play a major role in energy metabolism including lipid and glucose metabolism. Recent studies reported LXRs regulate plasma glucose although the mechanism is still uncertain. The present study investigated whether LXR activation regulates sodium glucose cotransporter2 (SGLT2) in human renal proximal tubular cells. LXR agonists, T0901317 and GW3965, inhibited SGLT2-mediated glucose uptake in concentration-dependent manners...
November 11, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/29126901/omega-3-polyunsaturated-fatty-acids-protect-human-hepatoma-cells-from-developing-steatosis-through-ffa4-gpr120
#6
Saeromi Kang, Jin Huang, Bo-Kyung Lee, Young-Suk Jung, Eunok Im, Jung-Min Koh, Dong-Soon Im
Protective effect of omega-3 polyunsaturated fatty acids (n-3 PUFA) on non-alcoholic fatty liver disease has been demonstrated. FFA4 (also known as GPR120; a G protein-coupled receptor) has been suggested to be a target of n-3 PUFA. FFA4 expression in hepatocytes has also been reported from liver biopsies in child fatty liver patients. In order to assess the functional role of FFA4 in hepatic steatosis, we used an in vitro model of liver X receptor (LXR)-mediated hepatocellular steatosis. FFA4 expression was confirmed in Hep3B and HepG2 human hepatoma cells...
November 7, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29115597/quantitative-proteomic-study-of-the-plasma-reveals-acute-phase-response-and-lxr-rxr-and-fxr-rxr-activation-in-the-chronic-unpredictable-mild-stress-mouse-model-of-depression
#7
Chuangchuang Yang, Chanjuan Zhou, Jie Li, Zhi Chen, Haiyang Shi, Wensong Yang, Yinhua Qin, Lin Lü, Libo Zhao, Liang Fang, Haiyang Wang, Zicheng Hu, Peng Xie
Major depressive disorder is a severe neuropsychiatric disease that negatively impacts the quality of life of a large portion of the population. However, the molecular mechanisms underlying depression are still unclear. The pathogenesis of depression involves several brain regions. However, most previous studies have focused only on one specific brain region. Plasma and brain tissues exchange numerous components through the blood‑brain barrier. Therefore, in the present study, plasma samples from control (CON) mice and mice subjected to chronic unpredictable mild stress (CUMS) were used to investigate the molecular pathogenesis of depression, and the association between the peripheral circulation and the central nervous system...
October 20, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29106686/the-identification-of-pivotal-transcriptional-factors-mediating-cell-responses-to-drugs-with-drug-induced-liver-injury-liabilities
#8
Falgun Shah, Alex Medvedev, Anne Mai Wassermann, Marian Brodney, Liying Zhang, Sergei Makarov, Robert V Stanton
Drug-induced liver injury (DILI) is a leading cause of drug attrition during drug development and a common reason for drug withdrawal from the market. The poor predictability of conventional animal-based approaches (Olson et al. 2000) necessitates the development of alternative testing approaches. Body of evidence associates DILI with the induction of stress-response genes in the liver cells (Yuan and Kaplowitz 2013). Here, we set out to identify signal transduction pathways predominantly involved in the regulation of gene transcription by DILI drugs...
November 2, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29097054/age-albumin-enhances-abca1-degradation-by-ubiquitin-proteasome-and-lysosomal-pathways-in-macrophages
#9
Rodrigo Tallada Iborra, Adriana Machado-Lima, Ligia Shimabukuro Okuda, Paula Ramos Pinto, Edna Regina Nakandakare, Ubiratan Fabres Machado, Maria Lucia Correa-Giannella, Russell Pickford, Tom Woods, Margaret A Brimble, Kerry-Anne Rye, Rui Lu, Shinji Yokoyama, Marisa Passarelli
BACKGROUND AND AIMS: Advanced glycation end products (AGEs) induce cellular oxidative/endoplasmic reticulum stress and inflammation. We investigated its underlying mechanisms for atherogenesis focusing on regulation of ABCA1 protein decay in macrophages. METHODS: The ABCA1 decay rate was evaluated in macrophages after treatment with LXR agonist and by incubation with control (C) or AGE-albumin concomitant or not with cycloheximide, MG-132, ammonium chloride and calpain inhibitors were utilized to inhibit, respectively, proteasome, lysosome and ABCA1 proteolysis at cell surface...
September 23, 2017: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/29068315/inhibition-of-cholesterol-biosynthesis-through-rnf145-dependent-ubiquitination-of-scap
#10
Li Zhang, Prashant Rajbhandari, Christina Priest, Jaspreet Sandhu, Xiaohui Wu, Ryan Temel, Antonio Castrillo, Thomas Q de Aguiar Vallim, Tamer Sallam, Peter Tontonoz
Cholesterol homeostasis is maintained through concerted action of the SREBPs and LXRs. Here, we report that RNF145, a previously uncharacterized ER membrane ubiquitin ligase, participates in crosstalk between these critical signaling pathways. RNF145 expression is induced in response to LXR activation and high-cholesterol diet feeding. Transduction of RNF145 into mouse liver inhibits the expression of genes involved in cholesterol biosynthesis and reduces plasma cholesterol levels. Conversely, acute suppression of RNF145 via shRNA-mediated knockdown, or chronic inactivation of RNF145 by genetic deletion, potentiates the expression of cholesterol biosynthetic genes and increases cholesterol levels both in liver and plasma...
October 25, 2017: ELife
https://www.readbyqxmd.com/read/29048364/protective-effect-of-argan-and-olive-oils-against-lps-induced-oxidative-stress-and-inflammation-in-mice-livers
#11
Soufiane El Kamouni, Riad El Kebbaj, Pierre Andreoletti, Abderrahim El Ktaibi, Issam Rharrassi, Abdelkhalid Essamadi, M'hammed Saïd El Kebbaj, Stéphane Mandard, Norbert Latruffe, Joseph Vamecq, Boubker Nasser, Mustapha Cherkaoui-Malki
Sepsis causes severe dysregulation of organ functions, via the development of oxidative stress and inflammation. These pathophysiological mechanisms are mimicked in mice injected with bacterial lipopolysaccharide (LPS). Here, protective properties of argan oil against LPS-induced oxidative stress and inflammation are explored in the murine model. Mice received standard chow, supplemented with argan oil (AO) or olive oil (OO) for 25 days, before septic shock was provoked with a single intraperitoneal injection of LPS, 16 hours prior to animal sacrifice...
October 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28993270/reduced-silent-information-regulator-1-signaling-exacerbates-sepsis-induced-myocardial-injury-and-mitigates-the-protective-effect-of-a-liver-x-receptor-agonist
#12
Dong Han, Xiang Li, Shuang Li, Tao Su, Li Fan, Wen-Si Fan, Hong-Yu Qiao, Jiang-Wei Chen, Miao-Miao Fan, Xiu-Juan Li, Ya-Bin Wang, Sai Ma, Ya Qiu, Zu-Hong Tian, Feng Cao
Myocardial injury and dysfunction are critical manifestations of sepsis. Previous studies have reported that liver X receptor (LXR) activation is protective during sepsis. However, whether LXR activation protects against septic heart injury and its underlying mechanisms remain elusive. This study was designed to determine the role of LXR activation in the septic heart with a focus on SIRT1 (silent information regulator 1) signaling. Male cardiac-specific SIRT1 knockout mice (SIRT1-/-) and their wild-type littermates were subjected to sepsis by cecal ligation and puncture (CLP) in the presence or absence of LXR agonist T0901317...
October 7, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28982861/liver-x-receptor-lxr-regulated-genes-of-cholesterol-trafficking-and-breast-cancer-severity
#13
COMPARATIVE STUDY
Christine Bobin-Dubigeon, Anaïs Chauvin, Victoire Brillaud-Meflah, Florence Boiffard, Marie-Pierre Joalland, Jean-Marie Bard
BACKGROUND: Liver X receptor [LXR; nuclear receptor subfamily 1, group H, member 2 (NR1H2, alias LXRB)] can inhibit proliferation and induce apoptosis of cancer cells. Its relationship with disease severity is not known. MATERIALS AND METHODS: Expression of LXRB, ATP binding cassette subfamily A member 1 (ABCA1), ATP binding cassette subfamily G member 1 (ABCG1), apolipoprotein E (APOE) and paraoxonase 2 (PON2) were determined in 69 breast tumors and were related to clinical stages of the disease and tumor characteristics, as well as time to recurrence...
October 2017: Anticancer Research
https://www.readbyqxmd.com/read/28971954/dbz-danshensu-bingpian-zhi-a-novel-natural-compound-derivative-attenuates-atherosclerosis-in-apolipoprotein-e-deficient-mice
#14
Jing Wang, Pengfei Xu, Xinni Xie, Jiao Li, Jun Zhang, Jialin Wang, Fan Hong, Jian Li, Youyi Zhang, Yao Song, Xiaohui Zheng, Yonggong Zhai
BACKGROUND: DBZ (Danshensu Bingpian Zhi), a synthetic derivative of a natural compound found in traditional Chinese medicine, has been reported to suppress lipopolysaccharide-induced macrophage activation and lipid accumulation in vitro. The aim of this study was to assess whether DBZ could attenuate atherosclerosis at early and advanced stages. METHODS AND RESULTS: The effects of DBZ on the development of atherosclerosis were studied using apolipoprotein E-deficient (apoE(-/-)) mice...
October 2, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28971895/dyslipidemia-alters-sperm-maturation-and-capacitation-in-lxr-null-mice
#15
Marjorie Whitfield, Rachel Guiton, Jeremie Rispal, Niyazi Acar, Ayhan Kocer, Joël R Drevet, Fabrice Saez
Lipid metabolism disorders (dyslipidemia) are causes of male infertility, but little is known about their impact on male gametes when considering post-testicular maturation events, given that studies concentrate most often on endocrine dysfunctions and testicular consequences. In this study, three-month-old wild type (wt) and Liver-X-Receptors knock out (Lxrα;β-/-) males were fed four weeks with a control or a lipid-enriched diet containing 1.25% cholesterol (High Cholesterol Diet - HCD). The HCD triggered a dyslipidemia leading to sperm post-testicular alterations and infertility...
October 2, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28969053/induction-of-socs3-by-liver-x-receptor-suppresses-the-proliferation-of-hepatocellular-carcinoma-cells
#16
Haojun Xiong, Yan Zhang, Shan Chen, Zhenhong Ni, Jintao He, Xinzhe Li, Bo Li, Kai Zhao, Fan Yang, Yijun Zeng, Bingbo Chen, Fengtian He
Liver X receptor (LXR), a member of nuclear receptor superfamily, is involved in the regulation of glucose, lipid and cholesterol metabolism. Recently, it has been reported that LXR suppress different kinds of cancers including hepatocellular carcinoma (HCC). However, the corresponding mechanism is still not well elucidated. In the present study, we found that activation of LXR downregulated cyclin D1 while upregulated p21 and p27 by elevating the level of suppressor of cytokine signaling 3 (SOCS3), leading to the cell cycle arrest at G1/S phase and growth inhibition of HCC cells...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28945911/hdl-cholesterol-efflux-capacity-in-newly-diagnosed-hiv-and-effects-of-antiretroviral-therapy
#17
Mabel Toribio, Min Hi Park, Markella V Zanni, Gregory K Robbins, Tricia H Burdo, Kenneth C Williams, Meghan N Feldpausch, Lauren Stone, Kathleen Melbourne, Steven K Grinspoon, Michael L Fitzgerald
Context: In the general population, high-density lipoprotein (HDL) cholesterol efflux capacity (HCEC) relates inversely to incident cardiovascular events. Previous studies have suggested that HCEC is decreased in HIV and that antiretroviral therapy (ART) initiation might improve HCEC. Objective: To evaluate HCEC in the context of ART initiation and immune activation in HIV. Design and Outcome Measures: Baseline HCEC from 10 ART-naive HIV-infected males and 12 prospectively matched non-HIV-infected males were analyzed...
November 1, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28944995/comparative-analysis-of-serum-proteome-in-congenital-scoliosis-patients-with-tbx6-haploinsufficiency-a-first-report-pointing-to-lipid-metabolism
#18
Qiankun Zhu, Nan Wu, Gang Liu, Yangzhong Zhou, Sen Liu, Jun Chen, Jiaqi Liu, Yuzhi Zuo, Zhenlei Liu, Weisheng Chen, Yixin Chen, Jia Chen, Mao Lin, Yanxue Zhao, Yang Yang, Shensgru Wang, Xu Yang, Yufen Ma, Jian Wang, Xiaoli Chen, Jianguo Zhang, Jianxiong Shen, Zhihong Wu, Guixing Qiu
Congenital scoliosis (CS) is a three-dimensional deformity of the spine affecting quality of life. We have demonstrated TBX6 haploinsufficiency is the most important contributor to CS. However, the pathophysiology at the protein level remains unclear. Therefore, this study was to explore the differential proteome in serum of CS patients with TBX6 haploinsufficiency. Sera from nine CS patients with TBX6 haploinsufficiency and nine age- and gender-matched healthy controls were collected and analysed by isobaric tagged relative and absolute quantification (iTRAQ) labelling coupled with mass spectrometry (MS)...
September 25, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28943908/expression-of-chicken-ovalbumin-upstream-promoter-transcription-factor-ii-and-liver-x-receptor-as-prognostic-indicators-for-human-colorectal-cancer
#19
Seong-Hoon Yun, Min-Gyoung Park, Yu-Mi Kim, Mee-Sook Roh, Joo-In Park
Cholesterol increases the risk of colorectal cancer. Liver X receptor (LXR), retinoid X receptor (RXR)α and sterol regulatory element binding protein (SREBP)-1c are transcriptional regulators of lipid metabolism. Chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) serves an essential role in angiogenesis and development, but its role in cancer is controversial. The expression of COUP-TFII, LXR, RXRα and SREBP-1c in colorectal cancer, as well as their association with clinicopathologic features, was assessed, and their utility as prognostic indicators in colorectal cancer evaluated...
October 2017: Oncology Letters
https://www.readbyqxmd.com/read/28943268/regulated-efflux-of-photoreceptor-outer-segment-derived-cholesterol-by-human-rpe-cells
#20
Federica Storti, Gabriele Raphael, Vera Griesser, Katrin Klee, Faye Drawnel, Carolin Willburger, Rebecca Scholz, Thomas Langmann, Arnold von Eckardstein, Jürgen Fingerle, Christian Grimm, Cyrille Maugeais
Genetic studies have linked age-related macular degeneration (AMD) to genes involved in high-density lipoprotein (HDL) metabolism, including ATP-binding cassette transporter A1 (ABCA1). The retinal pigment epithelium (RPE) handles large amounts of lipids, among others cholesterol, partially derived from internalized photoreceptor outer segments (OS) and lipids physiologically accumulate in the aging eye. To analyze the potential function of ABCA1 in the eye, we measured cholesterol efflux, the first step of HDL generation, in RPE cells...
September 21, 2017: Experimental Eye Research
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