2015 Annual Meeting Abstract Supplement Late-Breaking Abstract Submissions
Total Page：16
File Type：pdf, Size：1020Kb
Load more
Recommended publications
-
"This Is the Peer Reviewed Version of the Following Article: Murray, M., Dyari, H
"This is the peer reviewed version of the following article: Murray, M., Dyari, H. R. E., Allison, S. E. and Rawling, T. (2014), Lipid analogues as potential drugs for the regulation of mitochondrial cell death. British Journal of Pharmacology, 171: 2051–2066. doi: 10.1111/bph.12417 which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1111/bph.12417/abstract;jsessionid= 1A6A774DBD2AA9859B823125976041F6.f03t01 . This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving." 1 Revised manuscript 2013-BJP-0609-RCT-G Lipid analogues as potential drugs for the regulation of mitochondrial cell death Michael Murray1, Herryawan Ryadi Eziwar Dyari1, Sarah E. Allison1 and Tristan Rawling2 1Pharmacogenomics and Drug Development Group, Discipline of Pharmacology, University of Sydney, NSW 2006, Australia, and 2School of Pharmacy, Graduate School of Health, University of Technology, Sydney, PO Box 123, Broadway NSW 2007, Australia. Address for correspondence: Dr Michael Murray Pharmacogenomics and Drug Development Group, Discipline of Pharmacology, Medical Foundation Building, Room 105, University of Sydney, NSW 2006, Australia Tel: (61-2-9036-3259) Fax (61-2-9036-3244) Email: [email protected] Running title: Lipids drugs to target mitochondrial cell death 2 Abstract The mitochondrion has fundamental roles in the production of energy as ATP, the regulation of cell viability and apoptosis, and the biosynthesis of major structural and regulatory molecules, such as lipids. During ATP production reactive oxygen species are generated that alter the intracellular redox state and activate apoptosis. Mitochondrial dysfunction is a well recognized component of the pathogenesis of diseases such as cancer. -
Lipid Metabolic Reprogramming: Role in Melanoma Progression and Therapeutic Perspectives
cancers Review Lipid metabolic Reprogramming: Role in Melanoma Progression and Therapeutic Perspectives 1, 1, 1 2 1 Laurence Pellerin y, Lorry Carrié y , Carine Dufau , Laurence Nieto , Bruno Ségui , 1,3 1, , 1, , Thierry Levade , Joëlle Riond * z and Nathalie Andrieu-Abadie * z 1 Centre de Recherches en Cancérologie de Toulouse, Equipe Labellisée Fondation ARC, Université Fédérale de Toulouse Midi-Pyrénées, Université Toulouse III Paul-Sabatier, Inserm 1037, 2 avenue Hubert Curien, tgrCS 53717, 31037 Toulouse CEDEX 1, France; [email protected] (L.P.); [email protected] (L.C.); [email protected] (C.D.); [email protected] (B.S.); [email protected] (T.L.) 2 Institut de Pharmacologie et de Biologie Structurale, CNRS, Université Toulouse III Paul-Sabatier, UMR 5089, 205 Route de Narbonne, 31400 Toulouse, France; [email protected] 3 Laboratoire de Biochimie Métabolique, CHU Toulouse, 31059 Toulouse, France * Correspondence: [email protected] (J.R.); [email protected] (N.A.-A.); Tel.: +33-582-7416-20 (J.R.) These authors contributed equally to this work. y These authors jointly supervised this work. z Received: 15 September 2020; Accepted: 23 October 2020; Published: 27 October 2020 Simple Summary: Melanoma is a devastating skin cancer characterized by an impressive metabolic plasticity. Melanoma cells are able to adapt to the tumor microenvironment by using a variety of fuels that contribute to tumor growth and progression. In this review, the authors summarize the contribution of the lipid metabolic network in melanoma plasticity and aggressiveness, with a particular attention to specific lipid classes such as glycerophospholipids, sphingolipids, sterols and eicosanoids. -
Information to Users
INFORMATION TO USERS This manuscript has been reproduced from the microfilm master. UMI films the text directly from the original or copy submitted. Thus, some thesis and dissertation copies are in typewriter face, while others may be from any type of computer printer. The quality of this reproduction is dependent upon the quality of the copy submitted. Broken or indistinct print, colored or poor quality illustrations and photographs, print bleedthrough, substandard margins, and improper alignment can adversely affect reproduction. In the unlikely event that the author did not send UMI a complete manuscript and there are missing pages, these will be noted. Also, if unauthorized copyright material had to be removed, a note will indicate the deletion. Oversize materials (e.g., maps, drawings, charts) are reproduced by sectioning the original, beginning at the upper left-hand corner and continuing from left to right in equal sections with small overlaps. Each original is also photographed in one exposure and is included in reduced form at the back of the book. Photographs included in the original manuscript have been reproduced xerographically in this copy. Higher quality 6" x 9" black and white photographic prints are available for any photographs or illustrations appearing in this copy for an additional charge. Contact UMI directly to order. University Microfilms International A Bell & Howell Information Company 300 North Zeeb Road, Ann Arbor, Ml 48106-1346 USA 313/761-4700 800/521-0600 Order Number 0211150 The role of fatty acids and related analogs in mediating peroxisome proliferation in primary cultures of rat hepatocytes Intrasuksri, Urusa, Ph.D. -
![Etomoxir, Sodium 2-[6-(4Chlorophenoxy)Hexyl]Oxirane-2-Carboxylate, Increases Uncoupling Protein-3 Mrna Levels in Primary Culture](https://docslib.b-cdn.net/cover/8939/etomoxir-sodium-2-6-4chlorophenoxy-hexyl-oxirane-2-carboxylate-increases-uncoupling-protein-3-mrna-levels-in-primary-culture-2878939.webp)
Etomoxir, Sodium 2-[6-(4Chlorophenoxy)Hexyl]Oxirane-2-Carboxylate, Increases Uncoupling Protein-3 Mrna Levels in Primary Culture
Diabetes Publish Ahead of Print, published online April 28, 2008 PPARβ/δ prevents NF-κB activation in adipocytes Activation of Peroxisome Proliferator-Activated Receptor β/δ (PPARβ/δ) Inhibits LPS-induced Cytokine Production in Adipocytes by Lowering NF-κB Activity via ERK1/2 Ricardo Rodríguez-Calvo1, Lucía Serrano1, Teresa Coll1, Norman Moullan2, Rosa M. Sánchez1, Manuel Merlos1, Xavier Palomer1, Juan C. Laguna1, Liliane Michalik2, Walter Wahli2 and Manuel Vázquez-Carrera1. 1Pharmacology Unit, Department of Pharmacology and Therapeutic Chemistry, Faculty of Pharmacy, University of Barcelona, IBUB (Institut de Biomedicina de la UB), and CIBERDEM-Instituto de Salud Carlos III, Diagonal 643, E-08028 Barcelona, Spain and 2Center for Integrative Genomics, National Research Center Frontiers in Genetics, University of Lausanne, CH-1015 Lausanne, Switzerland. Corresponding author: Manuel Vázquez-Carrera Unitat de Farmacologia. Facultat de Farmàcia. Diagonal 643. E-08028 Barcelona. Spain E-mail: [email protected] Received for publication 07 February 2008 and accepted in revised form 21 April 2008. Copyright American Diabetes Association, Inc., 2008 PPARβ/δ prevents NF-κB activation in adipocytes Objective: Chronic activation of the nuclear factor (NF)-κB in white adipose tissue leads to increased production of pro-inflammatory cytokines, which are involved in the development of insulin resistance. It is presently unknown whether Peroxisome Proliferator-Activated Receptor (PPAR)β/δ activation prevents inflammation in adipocytes. Research Design and Methods and Results: Firstly, we examined whether the PPARβ/δ agonist GW501516 prevents LPS-induced cytokine production in differentiated 3T3-L1 adipocytes. Treatment with GW501516 blocked LPS-induced IL-6 expression and secretion by adipocytes and the subsequent activation of the STAT3-SOCS3 pathway. -
Role of PPAR and Its Agonist in Renal Diseases
Hindawi Publishing Corporation PPAR Research Volume 2010, Article ID 345098, 6 pages doi:10.1155/2010/345098 Review Article Role of PPARα and Its Agonist in Renal Diseases Ching-Feng Cheng,1, 2 Hsi-Hsien Chen,3 and Heng Lin4 1 Department of Medical Research, Tzu Chi General Hospital and Department of Pediatrics, Tzu Chi University, Hualien 970, Taiwan 2 Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan 3 Graduate Institute of Clinical Medicine, Taipei Medical University and Department of Internal Medicine, Taipei Medical University Hospital, Taipei 110, Taiwan 4 Graduate Institute of Pharmacology and Toxicology, Tzu Chi University, 701 Chung Yang Road, Section 3, Hualien 970, Taiwan Correspondence should be addressed to Heng Lin, [email protected] Received 17 June 2010; Accepted 17 October 2010 Academic Editor: Beatrice´ Desvergne Copyright © 2010 Ching-Feng Cheng et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Peroxisome proliferator-activated receptor (PPAR)-α, a member of a large nuclear receptor superfamily, plays a major role in the regulation of lipid metabolism. Recently, PPARα activation has been shown to confer additional benefits on endothelial function, kidney function, and anti-inflammation, suggesting that PPARα agonists may be good candidates for treating acute renal failure. In clinical application, PPAR-α activators, such as hypolipidemic drugs in fibric acid class, were proven to have therapeutic effects on metabolic syndrome and cardiovascular disease. This paper focuses on signaling pathways, ligand selectivity, and physio-pathological roles of PPARα in kidney diseases and the therapeutic utility of PPARα modulators in the treatment of diabetes and inflammation-induced nephropathy. -
Targeting Fatty Acid Oxidation to Promote Anoikis and Inhibit Ovarian Cancer Progression 2 3 4 Brandon T
Author Manuscript Published OnlineFirst on March 20, 2020; DOI: 10.1158/1541-7786.MCR-19-1057 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. 1 Targeting fatty acid oxidation to promote anoikis and inhibit ovarian cancer progression 2 3 4 Brandon T. Sawyer1, Lubna Qamar2, Tomomi M. Yamamoto2, Alexandra McMellen2, Zachary L. 5 Watson2, Jennifer K. Richer4, Kian Behbakht1, Isabel R. Schlaepfer#3, Benjamin G. Bitler#1,2 6 7 1Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of 8 Colorado School of Medicine, Aurora, CO, USA 9 2Division of Reproductive Sciences, Department of Obstetrics and Gynecology, University of 10 Colorado School of Medicine, Aurora, CO, USA 11 3Division of Medical Oncology, Department of Medicine, University of Colorado School of 12 Medicine, Aurora, CO, USA 13 4Department of Pathology, University of Colorado School of Medicine, Aurora, CO, USA 14 15 Running Title: FAO contributes to ovarian cancer dissemination 16 17 # Corresponding Authors: 18 19 Benjamin G. Bitler 20 Department of Obstetrics and Gynecology 21 University of Colorado Anschutz Medical Campus 22 12700 E. 19th Ave 23 MS 8613 24 Aurora, CO 80045 25 Phone: 303-724-0574 26 [email protected] 27 28 Isabel Schlaepfer 29 Department of Medical Oncology 30 University of Colorado Anschutz Medical Campus 31 12900 E. 19th Ave 32 MS 8117 33 Aurora, CO 80045 34 Phone: 303-724-4430 35 [email protected] 36 37 38 The authors declare no potential conflicts of interest. 39 40 Keywords: Ovarian cancer, Carnitine Palmitoyltransferase 1A, fatty acid beta oxidation, anoikis 41 resistance 42 43 Word Count: 5,535 44 45 Number of tables/figures: 4 figures 1 Downloaded from mcr.aacrjournals.org on September 28, 2021. -
Targeting Ppars
Natura Aonss Targeting PPARs: Coacatos Phamaceca Aonss Coeessos Anaonss/Paa Aonss A guide to function and structure PPAR α, δ, γ RR While PPARs display a high degree of homology at the protein level, each subtype exhibits distinct, noninter- PPRE DNA changeable roles in energy metabolism that range from energy burning to energy storage. Learn more about DA nn Hne Tage Gene ranscon their functions as fatty acid sensors and regulators of energy homeostasis at www.caymanchem.com/PPARs. www.caymanchem.com oman reon an nn oman A-1 A-2 NH2 COOH A/ C D E F MUSCLE PPARδ PPARα P se · ↑ Fatty acid oxidation · ↑ Fatty acid oxidation · ↑ Oxidative muscle fibers · ↑ Obesity resistance PPARγ PPARα* PPARδ PPARγ* · ↑ Insulin-mediated 1 99 173 239 466 468 1 71 145 211 439 441 1 136 210 238 503 505 · ↑ Insulin sensitivity glucose uptake A/ C D E F A/ C D E F A/ C D E F · ↑ Energy uncoupling Reesens sofom he canonca seence n nProt Reesens sofom he canonca seence n nProt FAAR NR1C2 Synonyms NR1C1 NR1C3 NUC1 LIVER PPARα PPARγ PPARβ · ↑ Fatty acid oxidation · ↑ Fatty acid storage · ↑ Ketogenesis · ↑ Lipogenesis CREBBP EP300 · ↓ Plasma triglycerides CITED2 FAM120B CREBBP MED1 (PBP/DRIP205/TRAP220) · ↑ Plasma HDL EP300 EP300 NCOA1 (RIP160/SRC-1) NCOA1 (RIP160/SRC-1) MED1 (PBP/DRIP205/TRAP220) NCOA2 (SRC-2) NCOA2 (SRC-2) Coactivators NCOA1 (RIP160/SRC-1) NCOA3 (SRC-3) NCOA3 (SRC-3) NCOA2 (SRC-2) NCOA4 PGC-1α NCOA3 (SRC-3) NCOA6 PGC-1α NCOA7 VESSEL WALL PPARα & PPARγ PGC-1β PGC-1α · ↓ Inflammation PRIC295 PGC-1β · ↑ Reverse cholesterol transport PGC-2 NCOR1 -
Role of Pparα and Its Agonist in Renal Diseases
Hindawi Publishing Corporation PPAR Research Volume 2010, Article ID 345098, 6 pages doi:10.1155/2010/345098 Review Article Role of PPARα and Its Agonist in Renal Diseases Ching-Feng Cheng,1, 2 Hsi-Hsien Chen,3 and Heng Lin4 1 Department of Medical Research, Tzu Chi General Hospital and Department of Pediatrics, Tzu Chi University, Hualien 970, Taiwan 2 Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan 3 Graduate Institute of Clinical Medicine, Taipei Medical University and Department of Internal Medicine, Taipei Medical University Hospital, Taipei 110, Taiwan 4 Graduate Institute of Pharmacology and Toxicology, Tzu Chi University, 701 Chung Yang Road, Section 3, Hualien 970, Taiwan Correspondence should be addressed to Heng Lin, [email protected] Received 17 June 2010; Accepted 17 October 2010 Academic Editor: Beatrice´ Desvergne Copyright © 2010 Ching-Feng Cheng et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Peroxisome proliferator-activated receptor (PPAR)-α, a member of a large nuclear receptor superfamily, plays a major role in the regulation of lipid metabolism. Recently, PPARα activation has been shown to confer additional benefits on endothelial function, kidney function, and anti-inflammation, suggesting that PPARα agonists may be good candidates for treating acute renal failure. In clinical application, PPAR-α activators, such as hypolipidemic drugs in fibric acid class, were proven to have therapeutic effects on metabolic syndrome and cardiovascular disease. This paper focuses on signaling pathways, ligand selectivity, and physio-pathological roles of PPARα in kidney diseases and the therapeutic utility of PPARα modulators in the treatment of diabetes and inflammation-induced nephropathy. -
Novel Mechanisms of CNS Fuel Sensing
UNIVERSITY OF CINCINNATI Date:___________________ I, _________________________________________________________, hereby submit this work as part of the requirements for the degree of: in: It is entitled: This work and its defense approved by: Chair: _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ Novel fuel sensing mechanisms in the regulation of food intake A dissertation submitted to the Division of Research and Advanced Studies of the University of Cincinnati in partial fulfillment of the requirements for the degree of DOCTORATE OF PHILOSOPHY (Ph.D.) in the Graduate Program in Neuroscience of the College of Medicine May 22, 2006 by Karine Proulx B.S., Université Laval, 2000 M.S., McGill University, 2002 Committee Chair: Randy J. Seeley, Ph.D. ABSTRACT An emerging model is that CNS fuel sensors, such as AMP kinase (AMPK) and the mammalian target of rapamycin (mTOR), integrate signals from stored and immediately available fuels, and in turn regulate food intake. The experiments described in this dissertation focus on novel CNS fuel sensing mechanisms by which fatty acid derivatives and compounds that affect fatty acid metabolism modulate food intake. Oleoylethanolamide (OEA), a derivative of oleic acid synthesized in the intestine following refeeding, reduces food intake. OEA shares similarities with other nutrient- derived hormones that signal energy status to the CNS, but its mechanisms of action remain unclear. We tested whether OEA-induced anorexia occurs through specific interactions with hormones that modulate food intake through CNS pathways involved in energy homeostasis, or is rather due to unspecific behaviors. Our results indicate that OEA suppresses feeding without causing visceral illness, and that neither ghrelin, PYY, GLP-1, apo A-IV nor CCK play a critical role in this effect. -
Peroxisome Proliferator-Activated Receptors (Ppars): Novel Therapeutic Targets in Renal Disease
CORE Metadata, citation and similar papers at core.ac.uk Provided by Elsevier - Publisher Connector Kidney International, Vol. 60 (2001), pp. 14–30 PERSPECTIVES IN BASIC SCIENCE Peroxisome proliferator-activated receptors (PPARs): Novel therapeutic targets in renal disease YOUFEI GUAN and MATTHEW D. BREYER Division of Nephrology, and Departments of Molecular Physiology and Biophysics, Veterans Administration Medical Center, and Vanderbilt University School of Medicine, Nashville, Tennessee, USA Peroxisome proliferator-activated receptors (PPARs): Novel inducers of hepatic peroxisomal proliferation. In rodents, therapeutic targets in renal disease. Peroxisome proliferator- chronic exposure to peroxisome proliferators results in activated receptors (PPARs) are members of the nuclear hor- nongenotoxic liver tumors [1] and alters gene expression mone receptor superfamily of ligand-dependent transcription  factors. PPARs play an important role in the general transcrip- involved in lipid -oxidation, cell differentiation and in- tional control of numerous cellular processes, including lipid flammation [2]. These effects are now known to be medi- metabolism, glucose homeostasis, cell cycle progression, cell ated through binding of peroxisome proliferators to a differentiation, inflammation and extracellular matrix remodel- specific subset of nuclear receptor and transcription fac- ␣  ing. Three PPAR isoforms, designated PPAR , PPAR and tor superfamily, designated peroxisome proliferator- PPAR␥, have been cloned and are differentially expressed in several tissues including the kidney. PPAR␣ primary regulates activated receptors (PPARs). Since the identification of lipid metabolism and modulates inflammation. PPAR␣ is the the first PPAR receptor in mouse [3], three isoforms— molecular target of the hypolipidemic fibrates including be- designated PPAR␣, PPAR/␦ and PPAR␥—have been zafibrate and clofibrate. PPAR participates in embryonic de- cloned and characterized by their distinct expression pat- ␥ velopment, implantation and bone formation. -
Fatty Acid Signaling in the -Cell and Insulin Secretion
Fatty Acid Signaling in the -Cell and Insulin Secretion Christopher J. Nolan,1 Murthy S.R. Madiraju,2 Viviane Delghingaro-Augusto,2 Marie-Line Peyot,2 and Marc Prentki2 Fatty acids (FAs) and other lipid molecules are important for many cellular functions, including vesicle exocytosis. For the pancreatic -cell, while the presence of some FAs is ree fatty acids (FFAs) are important to the essential for glucose-stimulated insulin secretion, FAs pancreatic -cell for its normal function, its have enormous capacity to amplify glucose-stimulated in- capacity to compensate for insulin resistance, sulin secretion, which is particularly operative in situa- and its failure in type 2 diabetes (1–3). Fatty acid tions of -cell compensation for insulin resistance. In this F (FA) deprivation of islet tissue causes loss of glucose- review, we propose that FAs do this via three interdepen- dent processes, which we have assigned to a “trident stimulated insulin secretion (GSIS), a process rapidly model” of -cell lipid signaling. The first two arms of the reversible by replacement with exogenous FFAs (4). In model implicate intracellular metabolism of FAs, whereas contrast, elevated FFA supply augments GSIS (5,6); how- the third is related to membrane free fatty acid receptor ever, if chronically in excess, particularly in association (FFAR) activation. The first arm involves the AMP-acti- with elevated glucose (7), saturated FFAs can reduce vated protein kinase/malonyl-CoA/long-chain acyl-CoA insulin biosynthesis (8) and secretion (3) and induce -cell (LC-CoA) signaling network in which glucose, together apoptosis (2,3,7,9). with other anaplerotic fuels, increases cytosolic malonyl- In this review, we consider the lipid signaling pathways CoA, which inhibits FA partitioning into oxidation, thus involved in the FFA modulation of GSIS in healthy -cells. -
Functional Analysis of Molecular and Pharmacological Modulators of Mitochondrial Fatty Acid Oxidation
www.nature.com/scientificreports OPEN Functional analysis of molecular and pharmacological modulators of mitochondrial fatty acid oxidation Yibao Ma1, Wei Wang1, Teja Devarakonda2, Huiping Zhou3, Xiang-Yang Wang4, Fadi N. Salloum2, Sarah Spiegel1 & Xianjun Fang1* Fatty acid oxidation (FAO) is a key bioenergetic pathway often dysregulated in diseases. The current knowledge on FAO regulators in mammalian cells is limited and sometimes controversial. Previous FAO analyses involve nonphysiological culture conditions or lack adequate quantifcation. We herein described a convenient and quantitative assay to monitor dynamic FAO activities of mammalian cells in physiologically relevant settings. The method enabled us to assess various molecular and pharmacological modulators of the FAO pathway in established cell lines, primary cells and mice. Surprisingly, many previously proposed FAO inhibitors such as ranolazine and trimetazidine lacked FAO-interfering activity. In comparison, etomoxir at low micromolar concentrations was sufcient to saturate its target proteins and to block cellular FAO function. Oxfenicine, on the other hand, acted as a partial inhibitor of FAO. As another class of FAO inhibitors that transcriptionally repress FAO genes, antagonists of peroxisome proliferator-activated receptors (PPARs), particularly that of PPARα, signifcantly decreased cellular FAO activity. Our assay also had sufcient sensitivity to monitor upregulation of FAO in response to environmental glucose depletion and other energy-demanding cues. Altogether this study provided a reliable FAO assay and a clear picture of biological properties of potential FAO modulators in the mammalian system. Fatty acid oxidation (FAO) is a key catabolic pathway for energy production in mammals1. Long-chain fatty acids are frst activated in the cytosol to fatty acyl-CoAs.