DOCSLIB.ORG

Gdf1 As a Regulator of Ceramide Metabolism and Hematopoiesis in Acute Myeloid Leukemia

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Gdf1 As a Regulator of Ceramide Metabolism and Hematopoiesis in Acute Myeloid Leukemia University of New Hampshire University of New Hampshire Scholars' Repository Doctoral Dissertations Student Scholarship Spring 2021 GDF1 AS A REGULATOR OF CERAMIDE METABOLISM AND HEMATOPOIESIS IN ACUTE MYELOID LEUKEMIA Weiyuan Wang University of New Hampshire, Durham Follow this and additional works at: https://scholars.unh.edu/dissertation Recommended Citation Wang, Weiyuan, "GDF1 AS A REGULATOR OF CERAMIDE METABOLISM AND HEMATOPOIESIS IN ACUTE MYELOID LEUKEMIA" (2021). Doctoral Dissertations. 2600. https://scholars.unh.edu/dissertation/2600 This Dissertation is brought to you for free and open access by the Student Scholarship at University of New Hampshire Scholars' Repository. It has been accepted for inclusion in Doctoral Dissertations by an authorized administrator of University of New Hampshire Scholars' Repository. For more information, please contact [email protected]. GDF1 AS A REGULATOR OF CERAMIDE METABOLISM AND HEMATOPOIESIS IN ACUTE MYELOID LEUKEMIA BY WEIYUAN WANG Master of Medicine, Shandong First Medical University, China, 2016 Bachelor of Medicine, Shandong First Medical University, China, 2013 DISSERTATION Submitted to the University of New Hampshire in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy in Molecular and Evolutionary Systems Biology May, 2021 ALL RIGHTS RESERVED © 2021 Weiyuan Wang ii GDF1 AS A REGULATOR OF CERAMIDE METABOLISM AND HEMATOPOIESIS IN ACUTE MYELOID LEUKEMIA BY WEIYUAN WANG This dissertation has been examined and approved in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Molecular and Evolutionary Systems Biology by: Dissertation Director, Brian Barth, Ph.D., Assistant Professor, Department of Molecular, Cellular and Biomedical Sciences Feixia Chu, Ph.D., Associate Professor, Department of Molecular, Cellular and Biomedical Sciences W. Kelley Thomas, Ph.D., Professor, Department of Molecular, Cellular and Biomedical Sciences Paul C. Tsang, Ph.D., Professor, Department of Molecular, Cellular and Biomedical Sciences Krisztina Varga, Ph.D., Associate Professor, Department of Molecular, Cellular and Biomedical Sciences On March 24, 2021 Approval signatures are on file with the University of New Hampshire Graduate School. iii ACKNOWLEDGEMENTS First, I would like to express my deepest appreciation to my advisor, Dr. Brian Barth, for taking me on as his first graduate student, offering me countless mentorship, and guiding me to achieve academic success throughout the years. In addition, I also appreciate his support in my daily life, such as picking me up at airports, taking the lab group and me to ice creams and lunches, and giving us surprises at our birthdays. Most importantly, I am thankful to him for always encouraging me to pursue a bigger dream. Second, I would like to thank my committee members. A big thank you goes to Dr. W. Kelley Thomas for introducing me to my doctoral advisor, offering me invaluable help in several classes, providing me with chances to meet guest professors, and guiding me through the doctoral defense. Many thanks go to Dr. Paul Tsang for being a role model in the lab which I teaching-assisted with him, being my reference when I applied for postdoc positions, writing recommendation letters for me, and guiding me through the doctoral defense. I am also grateful to Dr. Krisztina Varga for offering me invaluable help in her class, setting up the nicest neighbor lab, and guiding me through the defense. Lastly, I want to give special tribute to Dr. Feixia Chu for being a role model in the lab that I teaching-assisted with her, writing recommendation letters for me, and guiding me through the defense. Third, I would like to thank my teachers and colleagues who helped me throughout my doctoral study. First, I would like to express my deepest gratitude to my former advisor Qingliang Teng, who encouraged me to study abroad and from whom I learnt so much. A big thank you goes to Dr. Dean Elder and Dr. Linnea Morley for offering me tremendous support in the animal work and being my references when I applied for the postdoc position. Without their professional dedication, my research would definitely not be smooth. My gratitude also goes to iv Dr. Clyde Denis, Dr. Sarah Walker, and Dr. Xuanmao Chen, for giving me lots of invaluable advice. My sincere thank you goes to PhD candidate Melissa Kleinschmidt for all her selfless efforts and invaluable advice in helping me with all the writing assignments. I am very appreciative to Dr. David Plachetzki for being a wonderful program coordinator, writing recommendation letters for me, and guiding me through the PhD program. I am also grateful to Kristen Fuda for being a wonderful coordinator of my teaching lab. Last but not least, a huge thanks goes to the Office of International Students and Scholars at UNH for offering me so much help as an international student. I also would like to thank my lab mates who taught me the lab techniques, helped me overcome language barrier, and made my time in the lab such a pleasure. They are the postdoc Dr. Paul T. Toran; the graduate students including Kaitlyn C. Belknap, Vasiliki Papakotsi, and Devya Gurung; and the undergraduate students including Alexander J. Thorpe, Andrea L. Cote, Bert F. Prince, Emily C. Sullivan, Emma J. Arsenault, Jacqueline M. Marshall, Jacqueline M. Siciliano, Maria N. Clark, Mary A. Hurley, Noelle T. Labrecque, Sara E. Connell, and Tamara G. Hathorn. Special thanks go to Emma J. Arsenault, Alexander J. Thorpe, Andrea L. Cote, and Bert F. Prince for their invaluable help with editing the dissertation. I will always remember our happy times together. Last but not least, I would like to thank my friends and family. My friends include Yabin Zhang, Jonathan Sreter, Linghui Wu, Stefan Matissek, Weiguo Han, Xin Wang, Rongrong Yan, and Yixuan Gao. Without their unconditional support, I would not be able to persist till the end of the doctoral study. My family include my grandparents, aunts and uncles, cousins, and most importantly, my parents. Words cannot express my gratitude. To all I forgot to mention, I apologize. v Funding to support this research was provided to my dissertation advisor, Dr. Brian Barth, by the NIH/NCI through K22 CA190674, P01 CA171983, and R03 CA252825, as well as by the University of New Hampshire (UNH) COBRE Pilot Project Grant by NIH/NIGMS through P20 GM113131. The Department of Molecular, Cellular, and Biomedical Sciences of UNH helped fund my travel to several conferences. The Graduate School of UNH also helped fund my travel to several conferences and provided summer funding through the Summer Teaching Assistant Fellowship in 2019. vi TABLE OF CONTENTS ACKNOWLEDGEMENTS…........................................................................................................iv LIST OF TABLES..........................................................................................................................ix LIST OF FIGURES..........................................................................................................................x LIST OF ABBREVIATIONS........................................................................................................xii ABSTRACT................................................................................................................................ xvi CHAPTER PAGE 1. INTRODUCTION.....................................................................................................................1 1.1. Influences on the Hematopoietic Stem Cell Niche.........................................................1 1.2. Brief Overview of Hematologic Disorders..................................................................22 1.3. Epigenetics and Sphingolipid Metabolism in Health and Disease...............................43 1.4. Therapeutic Potential of Ceramides in Cancer Treatment............................................61 1.5. Regulation of Growth/Differentiation Factor 1 in Human and Animals......................81 1.6. Rationale and Significance of Thesis Research...........................................................93 1.7. Aims and Hypotheses of Individual Chapters..............................................................94 2. GDF1 REGULATES CERAMIDE DETOXIFICATION IN ACUTE MYELOID LEUKEMIA...................................................................................................................................95 2.1. Abstract.......................................................................................................................95 2.2. Introduction.................................................................................................................96 2.3. Results.........................................................................................................................97 2.4. Discussion.................................................................................................................103 2.5. Materials and Methods..............................................................................................105 vii 3. REGULATION OF HEMATOPOIESIS BY GDF1 IN ACUTE MYELOID LEUKEMIA……….....................................................................................................................110 3.1. Abstract.....................................................................................................................110 3.2. Introduction...............................................................................................................111
Load more

Recommended publications
  • Ceramide Metabolism Regulates a Neuronal Nadph Oxidase Influencing Neuron Survival During Inflammation
    Ceramide Metabolism Regulates A Neuronal Nadph Oxidase Influencing Neuron Survival During Inflammation Item Type Thesis Authors Barth, Brian M. Download date 07/10/2021 02:29:56 Link to Item http://hdl.handle.net/11122/8999 CERAMIDE METABOLISM REGULATES A NEURONAL NADPH OXIDASE INFLUENCING NEURON SURVIVAL DURING INFLAMMATION A THESIS Presented to the Faculty of the University of Alaska Fairbanks in Partial Fulfillment of the Requirements for the Degree of DOCTOR OF PHILOSOPHY By Brian M. Barth, B.S., M.S. Fairbanks, Alaska August 2009 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. UMI Number: 3386045 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. UMI Dissertation Publishing UMI 3386045 Copyright 2009 by ProQuest LLC. All rights reserved. This edition of the work is protected against unauthorized copying under Title 17, United States Code. ProQuest LLC 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106-1346 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. CERAMIDE METABOLISM REGULATES A NEURONAL NADPH OXIDASE INFLUENCING NEURON SURVIVAL DURING INFLAMMATION By Brian M. Barth RECOMMENDED: , ... f / M Advisory Committee Chah Chai ^Department of Chemistry and Biochemistry /? & f ) ./ APPROVED: Dean, C olleg£^ Natural Science'and“Mathemati cs /<C £>dan of the Graduate School 3 / / - Date Reproduced with permission of the copyright owner.
    [Show full text]
  • When a Slight Tilt Is Enough
    Cell. Mol. Life Sci. (2013) 70:181–203 DOI 10.1007/s00018-012-1038-x Cellular and Molecular Life Sciences REVIEW Ceramide function in the brain: when a slight tilt is enough Chiara Mencarelli • Pilar Martinez–Martinez Received: 11 January 2012 / Revised: 16 May 2012 / Accepted: 21 May 2012 / Published online: 24 June 2012 Ó The Author(s) 2012. This article is published with open access at Springerlink.com Abstract Ceramide, the precursor of all complex sphin- Introduction golipids, is a potent signaling molecule that mediates key events of cellular pathophysiology. In the nervous system, Ceramides are a family of lipid molecules that consist of the sphingolipid metabolism has an important impact. sphingoid long-chain base linked to an acyl chain via an Neurons are polarized cells and their normal functions, amide bond. Ceramides differ from each other by length, such as neuronal connectivity and synaptic transmission, hydroxylation, and saturation of both the sphingoid base rely on selective trafficking of molecules across plasma and fatty acid moieties. membrane. Sphingolipids are abundant on neural cellular Sphingoid bases are of three general chemical types: membranes and represent potent regulators of brain sphingosine, dihydrosphingosine (commonly known as homeostasis. Ceramide intracellular levels are fine-tuned ‘‘sphinganine’’, as it will be addressed in this review) and and alteration of the sphingolipid–ceramide profile con- phytosphingosine. Based on the nature of the sphingoid tributes to the development of age-related, neurological base backbone, we can distinguish three main subgroups in and neuroinflammatory diseases. The purpose of this the ceramide family: the compound named ceramide con- review is to guide the reader towards a better understanding tains sphingosine, which has a trans-double bond at the of the sphingolipid–ceramide pathway system.
    [Show full text]
  • Ceramide Kinase Is Upregulated in Metastatic Breast Cancer Cells and Contributes to Migration and Invasion by Activation of PI 3-Kinase and Akt
    International Journal of Molecular Sciences Article Ceramide Kinase Is Upregulated in Metastatic Breast Cancer Cells and Contributes to Migration and Invasion by Activation of PI 3-Kinase and Akt 1,2, 1, 2 2 Stephanie Schwalm y, Martin Erhardt y, Isolde Römer , Josef Pfeilschifter , Uwe Zangemeister-Wittke 1,* and Andrea Huwiler 1,* 1 Institute of Pharmacology, University of Bern, Inselspital, INO-F, CH-3010 Bern, Switzerland; [email protected] (S.S.); [email protected] (M.E.) 2 Institute of General Pharmacology and Toxicology, University Hospital Frankfurt am Main, Goethe-University, Theodor-Stern Kai 7, D-60590 Frankfurt am Main, Germany; [email protected] (I.R.); [email protected] (J.P.) * Correspondence: [email protected] (U.Z.-W.); [email protected] (A.H.); Tel.: +41-31-6323214 (A.H.) These authors contributed equally to this work. y Received: 29 November 2019; Accepted: 12 February 2020; Published: 19 February 2020 Abstract: Ceramide kinase (CerK) is a lipid kinase that converts the proapoptotic ceramide to ceramide 1-phosphate, which has been proposed to have pro-malignant properties and regulate cell responses such as proliferation, migration, and inflammation. We used the parental human breast cancer cell line MDA-MB-231 and two single cell progenies derived from lung and bone metastasis upon injection of the parental cells into immuno-deficient mice. The lung and the bone metastatic cell lines showed a marked upregulation of CerK mRNA and activity when compared to the parental cell line. The metastatic cells also had increased migratory and invasive activity, which was dose-dependently reduced by the selective CerK inhibitor NVP-231.
    [Show full text]
  • Suppression of Mast Cell Degranulation by a Novel Ceramide Kinase Inhibitor, the F-12509A Olefin Isomer K1
    Title Suppression of mast cell degranulation by a novel ceramide kinase inhibitor, the F-12509A olefin isomer K1 Kim, Jin-Wook; Inagaki, Yuichi; Mitsutake, Susumu; Maezawa, Nobuhiro; Katsumura, Shigeo; Ryu, Yeon-Woo; Park, Author(s) Chang-Seo; Taniguchi, Masaru; Igarashi, Yasuyuki Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 1738(1-3), 82-90 Citation https://doi.org/10.1016/j.bbalip.2005.10.007 Issue Date 2005 Doc URL http://hdl.handle.net/2115/5800 Type article (author version) File Information BBA1738(1-3).pdf Instructions for use Hokkaido University Collection of Scholarly and Academic Papers : HUSCAP 1 Suppression of mast cell degranulation by a novel ceramide kinase inhibitor, the F-12509A olefin isomer K1 Jin-Wook Kima, b, c, 1, Yuichi Inagakia, 1, Susumu Mitsutakea, Nobuhiro Maezawad, Shigeo Katsumurad, Yeon-Woo Ryub, Chang-Seo Parke, Masaru Taniguchif, and Yasuyuki Igarashia aDepartment of Biomembrane and Biofunctional Chemistry, Graduate School of Pharmaceutical Science, Hokkaido University. Kita 12, Nishi 6, Kita-ku, Sapporo 060-0812, Japan, bDepartment of Molecular Science and Technology, Ajou University, San 5, Wonchun-dong, Yeongtong-gu, Suwon 443-749, Korea, cDoosan Biotech, 39-3, Seongbok-dong, Yongin-si, Gyeonggi-do 449-795, Korea, dSchool of Science and Technology, Kwansei Gakuin University, Gakuen, Sanda, Hyogo 669-1337, Japan, eDepartment of Chemical and Biochemical Engineering, Dongguk University, 3-26 Pil-dong, Chung-gu, Seoul 100-715, Korea, fRIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa 230-0045, Japan Key words: ceramide, ceramide 1-phosphate, ceramide kinase, inhibitor, degranulation, mast cell To whom correspondence should be addressed: Dr.
    [Show full text]
  • Targeting the Sphingosine Kinase/Sphingosine-1-Phosphate Signaling Axis in Drug Discovery for Cancer Therapy
    cancers Review Targeting the Sphingosine Kinase/Sphingosine-1-Phosphate Signaling Axis in Drug Discovery for Cancer Therapy Preeti Gupta 1, Aaliya Taiyab 1 , Afzal Hussain 2, Mohamed F. Alajmi 2, Asimul Islam 1 and Md. Imtaiyaz Hassan 1,* 1 Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India; [email protected] (P.G.); [email protected] (A.T.); [email protected] (A.I.) 2 Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia; afi[email protected] (A.H.); [email protected] (M.F.A.) * Correspondence: [email protected] Simple Summary: Cancer is the prime cause of death globally. The altered stimulation of signaling pathways controlled by human kinases has often been observed in various human malignancies. The over-expression of SphK1 (a lipid kinase) and its metabolite S1P have been observed in various types of cancer and metabolic disorders, making it a potential therapeutic target. Here, we discuss the sphingolipid metabolism along with the critical enzymes involved in the pathway. The review provides comprehensive details of SphK isoforms, including their functional role, activation, and involvement in various human malignancies. An overview of different SphK inhibitors at different phases of clinical trials and can potentially be utilized as cancer therapeutics has also been reviewed. Citation: Gupta, P.; Taiyab, A.; Hussain, A.; Alajmi, M.F.; Islam, A.; Abstract: Sphingolipid metabolites have emerged as critical players in the regulation of various Hassan, M..I. Targeting the Sphingosine Kinase/Sphingosine- physiological processes. Ceramide and sphingosine induce cell growth arrest and apoptosis, whereas 1-Phosphate Signaling Axis in Drug sphingosine-1-phosphate (S1P) promotes cell proliferation and survival.
    [Show full text]
  • Ceramide Kinase and Ceramide-1-Phosphate
    Virginia Commonwealth University VCU Scholars Compass Theses and Dissertations Graduate School 2008 Ceramide Kinase and Ceramide-1-Phosphate Dayanjan Wijesinghe Virginia Commonwealth University Follow this and additional works at: https://scholarscompass.vcu.edu/etd Part of the Biochemistry, Biophysics, and Structural Biology Commons © The Author Downloaded from https://scholarscompass.vcu.edu/etd/1621 This Dissertation is brought to you for free and open access by the Graduate School at VCU Scholars Compass. It has been accepted for inclusion in Theses and Dissertations by an authorized administrator of VCU Scholars Compass. For more information, please contact [email protected]. © Dayanjan S Wijesinghe 2008 All Rights Reserved CERAMIDE KINASE AND CERAMIDE 1 PHOSPHATE A Dissertation submitted in partial fulfillment of the requirements for the degree of PhD at Virginia Commonwealth University. by DAYANJAN SHANAKA WIJESINGHE BSc., University of Peradeniya, Sri Lanka, 2001 Grad. I. Chem. C., Institute of Chemistry, Sri Lanka, 1998 Director: CHARLES E. CHALFANT ASSISTANT PROFFESSOR DEPARTMENT OF BIOCHEMISTRY AND MOLECULAR BIOLOGY Virginia Commonwealth University Richmond, Virginia December 2008 ii DEDICATION To my darling wife Piumini, my daughter Nisha, my Mother, Father and my Father and Mother-in-Law for their unconditional love and support. iii Acknowledgement I would like to express my heartfelt gratitude to my adviser, Dr. Charles E Chalfant for his guidance, counsel and advice without towards successful completion of this thesis. I am thankful to the members of my committee: Dr. Sarah Spiegel, Dr. Darrell L Peterson, Dr. Stephen T Sawyer and Dr. Lynne Elmore, for their valuable suggestions and time towards the successful completion of my degree.
    [Show full text]
  • Generation of Sphingosine-1-Phosphate Is Enhanced in Biliary Tract Cancer Patients and Is Associated with Lymphatic Metastasis
    www.nature.com/scientificreports OPEN Generation of sphingosine- 1-phosphate is enhanced in biliary tract cancer patients and Received: 5 April 2018 Accepted: 4 July 2018 is associated with lymphatic Published: xx xx xxxx metastasis Yuki Hirose1, Masayuki Nagahashi1, Eriko Katsuta2, Kizuki Yuza1, Kohei Miura1, Jun Sakata1, Takashi Kobayashi1, Hiroshi Ichikawa1, Yoshifumi Shimada1, Hitoshi Kameyama1, Kerry-Ann McDonald2, Kazuaki Takabe 1,2,3,4,5 & Toshifumi Wakai1 Lymphatic metastasis is known to contribute to worse prognosis of biliary tract cancer (BTC). Recently, sphingosine-1-phosphate (S1P), a bioactive lipid mediator generated by sphingosine kinase 1 (SPHK1), has been shown to play an important role in lymphangiogenesis and lymph node metastasis in several types of cancer. However, the role of the lipid mediator in BTC has never been examined. Here we found that S1P is elevated in BTC with the activation of ceramide-synthetic pathways, suggesting that BTC utilizes SPHK1 to promote lymphatic metastasis. We found that S1P, sphingosine and ceramide precursors such as monohexosyl-ceramide and sphingomyelin, but not ceramide, were signifcantly increased in BTC compared to normal biliary tract tissue using LC-ESI-MS/MS. Utilizing The Cancer Genome Atlas cohort, we demonstrated that S1P in BTC is generated via de novo pathway and exported via ABCC1. Further, we found that SPHK1 expression positively correlated with factors related to lymphatic metastasis in BTC. Finally, immunohistochemical examination revealed that gallbladder cancer with lymph node metastasis had signifcantly higher expression of phospho-SPHK1 than that without. Taken together, our data suggest that S1P generated in BTC contributes to lymphatic metastasis. Biliary tract cancer (BTC), the malignancy of the bile ducts and gallbladder, is a highly lethal disease in which a strong prognostic predictor is lymph node metastasis1–5.
    [Show full text]
  • Role of Ceramide Kinase in Breast Cancer Progression
    University of Pennsylvania ScholarlyCommons Publicly Accessible Penn Dissertations 2014 Role of Ceramide Kinase in Breast Cancer Progression Ania Warczyk Payne University of Pennsylvania, [email protected] Follow this and additional works at: https://repository.upenn.edu/edissertations Part of the Cell Biology Commons, Molecular Biology Commons, and the Pharmacology Commons Recommended Citation Payne, Ania Warczyk, "Role of Ceramide Kinase in Breast Cancer Progression" (2014). Publicly Accessible Penn Dissertations. 1402. https://repository.upenn.edu/edissertations/1402 This paper is posted at ScholarlyCommons. https://repository.upenn.edu/edissertations/1402 For more information, please contact [email protected]. Role of Ceramide Kinase in Breast Cancer Progression Abstract Recurrent breast cancer is typically an incurable disease and, as such, is disproportionately responsible for deaths from this disease. Recurrent breast cancers arise from the pool of disseminated tumor cells (DTCs) that survive adjuvant or neoadjuvant therapy, and patients with detectable DTCs following therapy are at substantially increased risk for recurrence. Consequently, the identification of pathways that contribute to the survival of breast cancer cells following therapy could aid in the development of more effective therapies that decrease the burden of residual disease and thereby reduce the risk of breast cancer recurrence. We now report that Ceramide Kinase (Cerk) is required for mammary tumor recurrence following HER2/neu pathway inhibition and is spontaneously up-regulated during tumor recurrence in multiple genetically engineered mouse models for breast cancer. We find that Cerk is apidlyr up-regulated in tumor cells following HER2/neu down-regulation or treatment with adriamycin and that Cerk is required for tumor cell survival following HER2/neu down-regulation.
    [Show full text]
  • Macedonian Journal of Medical Sciences
    ID Design 2012/DOOEL Skopje Open Access Macedonian Journal of Medical Sciences. 2015 Mar 15; 3(1):18-25. http://dx.doi.org/10.3889/oamjms.2015.030 Basic Science Serum Ceramide Kinase as a Biomarker of Cognitive Functions, and the Effect of Using Two Slimming Dietary Therapies in Obese Middle Aged Females Maha I. A. Moaty1*, Suzanne Fouad1, Salwa M. El Shebini1, Yusr M. I. Kazem1, Nihad H. Ahmed1, Magda S. Mohamed1, Ahmed M. S. Hussein2, Atiat M. Arafa1, Laila M. Hanna1, Salwa T. Tapozada1 1Nutrition and Food Science Department, National Research Centre, Dokki, Giza, Egypt; 2Food Technology Department, National Research Centre, Dokki, Giza, Egypt (Affiliation ID: 60014618) Abstract Citation: Moaty MIA, Fouad S, El Shebini SM, Kazem AIM: Highlighting the impact of obesity on mental and cognitive functions using serum ceramide YMI, Ahmed NH, Mohamed MS, Hussein AMS, Arafa AM, Hanna LM, Tapozada ST. Serum Ceramide Kinase as a kinase enzyme concentration as a biomarker for cognitive evaluation in the middle aged females, Biomarker of Cognitive Functions, and the Effect of Using and also targeting to control the obesity and simultaneously postponing the deterioration of the Two Slimming Dietary Therapies in Obese Middle Aged Females. OA Maced J Med Sci. 2015 Mar 15; 3(1):18-25. cognitive functions, by implementing two slimming dietary therapies each incorporating different http://dx.doi.org/10.3889/oamjms.2015.030 functional ingredients known to boost cognition. Key words: Cognitive function; ceramide kinase enzyme; obesity; dietary therapy; middle aged females. SUBJECTS AND METHODS: Ninety six obese middle aged females, divided into two groups *Correspondence: Maha Ibrahim Abdel Moaty (Maha I.
    [Show full text]
  • Ceramide 1-Phosphate/Ceramide, a Switch Between Life and Death ⁎ Antonio Gómez-Muñoz
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Biochimica et Biophysica Acta 1758 (2006) 2049–2056 www.elsevier.com/locate/bbamem Review Ceramide 1-phosphate/ceramide, a switch between life and death ⁎ Antonio Gómez-Muñoz Department of Biochemistry and Molecular Biology. Faculty of Science and Technology. University of the Basque Country. P.O. Box 644. 48080-Bilbao, Spain Received 13 February 2006; received in revised form 4 May 2006; accepted 11 May 2006 Available online 19 May 2006 Abstract Ceramide is a well-characterized sphingolipid metabolite and second messenger that participates in numerous biological processes. In addition to serving as a precursor to complex sphingolipids, ceramide is a potent signaling molecule capable of regulating vital cellular functions. Perhaps its major role in signal transduction is to induce cell cycle arrest, and promote apoptosis. In contrast, little is known about the metabolic or signaling pathways that are regulated by the phosphorylated form of ceramide. It was first demonstrated that ceramide-1-phosphate (C1P) had mitogenic properties, and more recently it has been described as potent inhibitor of apoptosis and inducer of cell survival. C1P and ceramide are antagonistic molecules that can be interconverted in cells by kinase and phosphatase activities. An appropriate balance between the levels of these two metabolites seems to be crucial for cell and tissue homeostasis. Switching this balance towards accumulation of one or the other may result in metabolic dysfunction, or disease. Therefore, the activity of the enzymes that are involved in C1P and ceramide metabolism must be efficiently coordinated to ensure normal cell functioning.
    [Show full text]
  • Sphingolipids in High Fat Diet and Obesity-Related Diseases
    Hindawi Publishing Corporation Mediators of Inflammation Volume 2015, Article ID 520618, 12 pages http://dx.doi.org/10.1155/2015/520618 Review Article Sphingolipids in High Fat Diet and Obesity-Related Diseases Songhwa Choi1,2 and Ashley J. Snider1,2,3 1 Department of Medicine and Molecular and Cellular Biology, Stony Brook University, Stony Brook, NY 11794, USA 2Stony Brook Cancer Center, Stony Brook University, Stony Brook, NY 11794, USA 3Northport VA Medical Center, Northport, NY 11768, USA Correspondence should be addressed to Ashley J. Snider; [email protected] Received 14 August 2015; Accepted 18 October 2015 Academic Editor: Marc Pouliot Copyright © 2015 S. Choi and A. J. Snider. 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. Nutrient oversupply associated with a high fat diet (HFD) significantly alters cellular metabolism, and specifically including sphingolipid metabolism. Sphingolipids are emerging as bioactive lipids that play key roles in regulating functions, in addition to their traditional roles as membrane structure. HFD enhances de novo sphingolipid synthesis and turnover of sphingolipids via the salvage pathway, resulting in the generation of ceramide, and more specifically long chain ceramide species. Additionally, HFD elevates sphingomyelin and sphingosine-1 phosphate (S1P) levels in several tissues including liver, skeletal muscle, adipose tissue, and cardiovascular tissues. HFD-stimulated sphingolipid generation contributes to systemic insulin resistance, dysregulated lipid accumulation, and cytokine expression and secretion from skeletal muscle and adipose tissues, exacerbating obesity-related conditions. Furthermore, altered sphingolipid levels, particularly ceramide and sphingomyelin, are involved in obesity-induced endothelial dysfunction and atherosclerosis.
    [Show full text]
  • Trafficking and Functions of Bioactive Sphingolipids
    Journal name: Lipid Insights Journal type: Review Year: 2015 Volume: 8(S1) Trafficking and Functions of Bioactive Sphingolipids: Running head verso: Zhou and Blom Lessons from Cells and Model Membranes Running head recto: Lessons from cells and model membranes Supplementary Issue: Cellular Anatomy of Lipid Traffic Kecheng Zhou and Tomas Blom Department of Anatomy, Faculty of Medicine, University of Helsinki, Helsinki, Finland. ABSTRACT: Ceramide and sphingosine and their phosphorylated counterparts are recognized as “bioactive sphingolipids” and modulate membrane integrity, the activity of enzymes, or act as ligands of G protein-coupled receptors. The subcellular distribution of the bioactive sphingolipids is central to their function as the same lipid can mediate diametrically opposite effects depending on its location. To ensure that these lipids are present in the right amount and in the appropriate organelles, cells employ selective lipid transport and compartmentalize sphingolipid-metabolizing enzymes to characteristic subcellular sites. Our knowledge of key mechanisms involved in sphingolipid signaling and trafficking has increased substantially in the past decades— thanks to advances in biochemical and cell biological methods. In this review, we focus on the bioactive sphingolipids and discuss how the combination of studies in cells and in model membranes have contributed to our understanding of how they behave and function in living organisms. KEYWORDS: ceramide, sphingosine, ceramide 1-phosphate, sphingosine 1-phosphate, membrane, lipid trafficking SUPPLEMENT: Cellular Anatomy of Lipid Traffic COMPETING INTERESTS: Authors disclose no potential conflicts of interest. CITATION: Zhou and Blom. Trafficking and Functions of Bioactive Sphingolipids: Lessons COPYRIGHT: © the authors, publisher and licensee Libertas Academica Limited. from Cells and Model Membranes.
    [Show full text]