DOCSLIB.ORG

Colombian Guidelines for Diagnosis of Lipase Acid Deficiency

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Colombian Guidelines for Diagnosis of Lipase Acid Deficiency DOI: https://doi.org/10.22516/25007440.180 Review articles Colombian Guidelines for Diagnosis of Lipase Acid Deficiency Alfredo Santamaría Escobar,1 Carolina Baquero Montoya,2 Roberto García Bermejo,3 Adriana María Jaramillo Villegas,4 Armando Barrios,5 Mauricio Coll Barrios,6 Rodrigo de Vivero Camacho,7 Rocío del Pilar López Panqueva,8 William Márquez,9 Diana Victoria Mora Quintero,10 Omar Pérez Álvarez,11 Carolina Rivera Nieto,12 Evelyn Simancas Escalante,13 Giomar Sarmiento Marengo,14 Luis Carlos Ramírez Urrego,15 Patricia Ruiz Navas,16 Claudia Sánchez Franco,17 David Alfonso Suárez Zamora,18 Verónica Botero.19 1 Hospital Universitario San Vicente Fundación in Abstract Medellín, Colombia 2 Hospital Pablo Tobón Uribe in Medellín, Colombia Introduction: Lysosomal acid lipase deficiency (LAL-D) is an inherited autosomal recessive entity that leads 3 Hospital Infantil Napoleón Franco Pareja, Universidad to the accumulation of cholesterol and triglyceride esters in the liver, spleen and other organs. The age of del Sinú in Cartagena, Colombia onset and rate of progression vary greatly, possibly explained by mutations of the LIPA gene. Clinical ma- 4 Clínicas Las Américas in Medellín, Antioquia, Colombia nifestations are the same as those of other hepatic, cardiovascular and metabolic pathologies which makes 5 Pediatric Gastroenterology Unit of Cesar in it difficult to recognize in clinical practice. Objective: The objectives of these guidelines is to help clinicians Valledupar, Colombia recognize the major groups at risk for LAL-D and to improve its diagnosis. Methodology: This document was 6 Centro Médico Almirante Colón in Bogotá, Colombia 7 Pediatric Departament of the Hospital Infantil designed as a consensus of experts in gastroenterology, hepatology, endocrinology, genetics, pathology and Napoleón Franco Pareja and the Universidad de pediatrics. A review of the literature regarding clinical manifestations and tools for diagnosis of LAL-D was Cartagena in Cartagena, Colombia conducted and the nominal group technique was followed. Results: Diagnostic algorithms which facilitate 8 Hospital Universitario Fundación Santa Fe de Bogotá and Universidad de los Andes in Bogotá Colombia suspicion and diagnosis of LAL-D were generated by consensus for each of the risk groups. Conclusions: 9 Fundación Hospital de la Misericordia in Bogotá, This guide proposes algorithms for the diagnosis of LAL-D based on clinical consensus. The algorithms seek Colombia to optimize diagnosis for patients with this pathology. 10 Fundación Hospital de la Misericordia in Bogotá Colombia 11 Clínica la Misericordia in Barranquilla, Colombia Keywords 12 Fundación Cardio-Infantil in Bogotá, Colombia Acid lipase deficiency, cholesterol ester deposition disease, Wolman’s disease, dyslipidemia, hepatomegaly. 13 Hospital San Juan de Sahagún in Sahagún, Córdoba, Colombia 14 Hospital Universitario Fernando Troconis in Santa Marta, Magdalena, Colombia 15 Unidad Materno Infantil del Tolima at the Hospital Federico Lleras Acosta in Ibagué, Tolima, Colombia 16 Hospital Pablo Tobón Uribe in Medellín, Colombia 17 Fundación Hospital de la Misericordia in Bogotá, Colombia 18 Hospital Universitario Fundación Santa Fe de Bogotá in Bogotá Colombia 19 Fundación Valle del Lili in Cali, Colombia ......................................... Received: 04-04-17 Accepted: 06-10-17 INTRODUCTION criteria and autonomy but to be useful guides for clinical decision-making. This guide was the result of a consensus Guidelines and expert consensuses are documents that aim of 20 experts from several medical specialties. to help doctors evaluate the benefits and risks of diagnos- Each group of specialists conducted an exhaustive search tic and therapeutic procedures related to a specific patho- of the available evidence in the current medical literature logy. These documents are not intended to replace medical in PubMed and LILACS, the most frequently used search 358 © 2017 Asociaciones Colombianas de Gastroenterología, Endoscopia digestiva, Coloproctología y Hepatología engines. Then the group reviewed and synthesized the evi- This guide was developed by a committee of experts in dence which became the basis for the expert consensus. pediatrics, pediatric gastroenterology, pediatric endocri- Each group prepared a document on a related theme which nology, hepatology, pathology and genetics using nomi- was sent via e-mail to all the experts for their knowledge, nal group technique (NGT). Based on their experience analysis and contributions. The experts then presented and a wide literature review, the experts debated and dis- the best available evidence on the diagnostic criteria for cussed their different points of view to arrive at a list of LAL-D in each risk group at a face-to-face scientific con- recommendations representing their collective judgment. ference. This was followed by a debate in which each par- The objective was to propose guidelines that can be used ticipant was able to express her or his opinion. Once the in clinical practice for identification of patients with this discussion points were analyzed. Consensus was defined as pathology in Colombia. agreement of more than 80% of the members. Once con- sensus was reached, a report was issued with the recom- PHYSIOPATHOLOGY mendations and the design of algorithms that defined the path for the diagnosis of this pathology for the risk groups LAL-D originates in mutations of the LIPA gene located at under consideration. This was the responsibility of the con- 10q23.2. It has 10 exons and an approximate length of 45 sensus coordinators. This document was then provided to kilobases (kb). (1) This entity is autosomal recessive inhe- all participants and consensus was reached. ritance whose most common defect is associated with a LAL-D (OMIM 278000) is an autosomal recessive mutation at the site of exon 8 (c.894G> A) which is known disease caused by mutations in the LIPA gene that dras- as E8SJM. This mutation is present in about half of the affec- tically reduce the activity of the lysosomal acid lipase ted patients, (12) To date, more than 40 mutations which enzyme (LAL, EC 3.1.1.13). (1) This enzyme is responsi- lead to alterations of the enzyme’s function and which are ble for breaking down cholesterol esters and triglycerides, related to this pathology have been described. (2) The most so dysfunction leads to their accumulation in the liver, drastic ones are nonsense and frameshift mutations which spleen, macrophages and other organs. (2) The disease are usually associated with severely affected patients, while is characterized by microvesicular steatosis that produces cases in children and adults are associated with mutations liver failure, elevation of serum transaminases, accelerated whose effects on the protein are not as dramatic. (13) atherosclerosis and premature death. (3) Infantile presen- The LAL enzyme plays a key role in the metabolism of tation was described in 1956, and this disease was histo- lipids since it is responsible for hydrolysis of cholesterol rically called Wolman’s disease. (4) It is characterized by esters and triglycerides within lysosomes. (14) The action of vomiting, diarrhea, failure to thrive and hepatosplenome- this enzyme generates free cholesterol which is involved in galy (HSM) with rapid deterioration of liver functioning negative regulation of LDL receptors, in the inhibition of the and death at an average age of 3.7 months. (5) The late 3-hydroxy-3-methylglutaryl-coenzyme A reductase which onset form was known as cholesterol ester deposit disease is a rate controlling enzyme, and in the stimulation of acyl- and was first described in 1963. (6) It has a broad clinical coenzyme A (CoA):cholesterol acyltransferase (ACAT). spectrum and can occur in infants, children or adults. (7) Congenital deficiencies of this enzyme lead to lysosomal It is usually underdiagnosed and presents with liver com- accumulation of cholesterol and triglyceride esters and to promise, elevated transaminases and elevated serum levels failure of the LDL receptor pathway. Therefore, in addition of LDL (low density lipoprotein) cholesterol and triglyce- to this massive lysosomal accumulation of cholesterol esters, rides with normal or low levels of HDL cholesterol (high there is a systemic increase in synthesis of cholesterol. (15) density lipoprotein). Early death is due to hepatic insuffi- ciency or accelerated atherosclerosis secondary to chronic CLINICAL PICTURE hyperlipidemia. (2) Incidence has been estimated from genetic studies at Acid lipase deficiencies have a wide range of phenotypic 1/40,000 while the approximate incidence of the most presentations which manifest in very early childhood, in severe forms is 1/500,000. (8, 9, 10) Given its nonspecific later childhood or in later stages of life. clinical presentation and the relatively low number of publis- hed cases, it is believed that this entity has a high index of Presentation in Infants underdiagnoses. (11) For this reason, these guidelines have been developers to offer health-care personnel a series of LAL-D usually manifests with the most acute symptoms recommendations to guide themselves in developing suspi- when it manifests in the first days of life. Gastrointestinal cion of LAL-D and the ability to correctly diagnose it. symptoms include vomiting, diarrhea, steatorrhea, and Colombian Guidelines for Diagnosis of Lipase Acid Deficiency 359 abdominal distension secondary to hepatosplenomegaly. total lipase activity with lipase activity in the presence In
Load more

Recommended publications
  • Avicin G Is a Potent Sphingomyelinase Inhibitor and Blocks Oncogenic K- and H-Ras Signaling Christian M
    www.nature.com/scientificreports OPEN Avicin G is a potent sphingomyelinase inhibitor and blocks oncogenic K- and H-Ras signaling Christian M. Garrido1, Karen M. Henkels1, Kristen M. Rehl1, Hong Liang2, Yong Zhou2, Jordan U. Gutterman3 & Kwang-jin Cho1 ✉ K-Ras must interact primarily with the plasma membrane (PM) for its biological activity. Therefore, disrupting K-Ras PM interaction is a tractable approach to block oncogenic K-Ras activity. Here, we found that avicin G, a family of natural plant-derived triterpenoid saponins from Acacia victoriae, mislocalizes K-Ras from the PM and disrupts PM spatial organization of oncogenic K-Ras and H-Ras by depleting phosphatidylserine (PtdSer) and cholesterol contents, respectively, at the inner PM leafet. Avicin G also inhibits oncogenic K- and H-Ras signal output and the growth of K-Ras-addicted pancreatic and non-small cell lung cancer cells. We further identifed that avicin G perturbs lysosomal activity, and disrupts cellular localization and activity of neutral and acid sphingomyelinases (SMases), resulting in elevated cellular sphingomyelin (SM) levels and altered SM distribution. Moreover, we show that neutral SMase inhibitors disrupt the PM localization of K-Ras and PtdSer and oncogenic K-Ras signaling. In sum, this study identifes avicin G as a new potent anti-Ras inhibitor, and suggests that neutral SMase can be a tractable target for developing anti-K-Ras therapeutics. Ras proteins are small GTPases that primarily localize to the inner-leafet of the plasma membrane (PM), switch- ing between an active GTP-bound state and inactive GDP-bound state1. In response to epidermal growth factor stimulation or receptor tyrosine kinase activation, guanine nucleotide exchange factors activate Ras by inducing the release of the guanine nucleotides and binding of GTP1.
    [Show full text]
  • Autophagy As a Promoter of Longevity – Insights from Model Organisms
    1 2 3 4 Autophagy as a promoter of longevity – insights from model organisms 5 Malene Hansen1, David C. Rubinsztein2,3, and David W. Walker4,5 6 7 8 1Sanford Burnham Prebys Medical Discovery Institute, Program of Development, Aging and 9 Regeneration, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA. 10 2Cambridge Institute for Medical Research, Department of Medical Genetics; 11 3UK Dementia Research Institute, University of Cambridge, Hills Road, Cambridge CB2 0XY, 12 UK. 13 4 Department of Integrative Biology and Physiology, University of California, Los Angeles, CA 14 90095, USA; 15 5Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA. 16 17 Correspondence: 18 MH ([email protected]), DWW ([email protected]), DCR ([email protected]) 19 20 Keywords: 21 Selective autophagy, tissue specificity, pathophysiology, ageing, S. cerevisiae, C. elegans, 22 Drosophila 23 24 1 25 Glossary 26 Aggrephagy: The selective removal of cytosolic aggregates by autophagy. 27 28 Autophagosome: A cytosolic double membrane-bound vesicle, capable of sequestering 29 cytoplasmic inclusions and organelles destined for degradation in the autolysosome. 30 31 Autolysosome: A cytosolic vesicle resulting from fusion between an autophagosome and 32 acidic lysosomes in which degradation of the inner membrane and sequestered material in the 33 autophagosome takes place. 34 35 Glomerulus: A key structure of a nephron, the functional unit of the kidney. 36 37 Hormesis/Hormetic heat shock: Beneficial effects of a treatment that at a higher intensity is 38 harmful. In one form of hormesis, non-lethal exposure to elevated temperature induces a 39 response that results in increased stress resistance and longevity.
    [Show full text]
  • Regulation of Microvesicle Particle Release in Keratinocytes
    Wright State University CORE Scholar Browse all Theses and Dissertations Theses and Dissertations 2018 Regulation of Microvesicle Particle Release in Keratinocytes Azeezat Afolake Awoyemi Wright State University Follow this and additional works at: https://corescholar.libraries.wright.edu/etd_all Part of the Pharmacology, Toxicology and Environmental Health Commons Repository Citation Awoyemi, Azeezat Afolake, "Regulation of Microvesicle Particle Release in Keratinocytes" (2018). Browse all Theses and Dissertations. 1999. https://corescholar.libraries.wright.edu/etd_all/1999 This Thesis is brought to you for free and open access by the Theses and Dissertations at CORE Scholar. It has been accepted for inclusion in Browse all Theses and Dissertations by an authorized administrator of CORE Scholar. For more information, please contact [email protected]. REGULATION OF MICROVESICLE PARTICLE RELEASE IN KERATINOCYTES A thesis submitted in partial fulfilment of the Requirements for the degree of Master of Science By AZEEZAT AFOLAKE AWOYEMI B.S., University of Lagos, 2015 2018 Wright State University i All rights reserved. This work may not be reproduced in whole or in part by photocopy or other means, without permission of the author. COPYRIGHT BY AZEEZAT AFOLAKE AWOYEMI 2018 ii WRIGHT STATE UNIVERSITY GRADUATE SCHOOL JULY 23, 2018 I HEREBY RECOMMEND THAT THE THESIS PREPARED UNDER MY SUPERVISION BY Azeezat Afolake Awoyemi ENTITLED Regulation of Microvesicle Particle release in keratinocytes. BE ACCEPTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF Master of Science. Jeffrey B. Travers, M.D., Ph.D. Thesis Director Jeffrey B. Travers, M.D., Ph.D. Chair, Department of Pharmacology and Toxicology Committee on Final Examination Jeffrey B Travers, M.D., Ph.D.
    [Show full text]
  • Scientific Report 2012 Ongoing Research 2013
    SCIENTIFIC REPORT 2012 ONGOING RESEARCH 2013 IRCCS “Istituto Giannina Gaslini” Via Gerolamo Gaslini, 5 16147 Genova – Italy Tel. +39 010 5636 806/807 Fax +39 010 3776590 e-mail: [email protected] www.gaslini.org Some pictures of the Istituto Giannina Gaslini Nobel laureates at Gaslini: Renato Dulbecco and Rolf Zinkernagel Pope Benedict XVI visiting Gaslini Monsignor Angelo Bagnasco visiting Gaslini Some moments of the visit of the International Scientific Committee (Professors Alain Fischer, Max Cooper, Sergio Romagnani and Anthony Fauci) Annual Meeting of the SIOP Brain Tumor Sub-Committee The Germana International Centre for Studies and training (CISEF): a center of excellence which carries out educational activities in the fields of scientific research, prediatrics, organization and quality of health care services. TRIPR (Translational Research in Pediatric Rheumatology) Congress 2009 The 2 nd Training Course on Blood and Marrow Trasplantation: a course of paediatricians and pediatric nurses on HSCT in children and adolescents “I am not a man of science, but I am perfectly aware that only by starting from scientific research, conducted under proper direction, can physicians conscientiously accomplish their difficult task” (Gerolamo Gaslini) Foreword A recent publication by Via Academy - “Small is beautiful” – analyzed the quality of research carried out in different Italian universities and institutes. Small and medium-sized organizations with fewer than 100 principal investigators (PI) or university professors were extracted and in this ranking, based on the ratio of PI/TIS (Top Italian Scientists, Via Academy), Gaslini is ranked first, closely above the Humanitas Institute of Milan. This is a remarkable result and underscores once more the caliber of Gaslini’s researchers, among whom 23 are TIS, equally distributed between basic and clinical investigators.
    [Show full text]
  • Role of Acid Sphingomyelinase and IL-6 As Mediators Of
    Thorax Online First, published on July 27, 2016 as 10.1136/thoraxjnl-2015-208067 Respiratory research ORIGINAL ARTICLE Thorax: first published as 10.1136/thoraxjnl-2015-208067 on 27 July 2016. Downloaded from Role of acid sphingomyelinase and IL-6 as mediators of endotoxin-induced pulmonary vascular dysfunction Rachele Pandolfi,1,2,3 Bianca Barreira,1,2,3 Enrique Moreno,1,2,3 Victor Lara-Acedo,2 Daniel Morales-Cano,1,2,3 Andrea Martínez-Ramas,1,2,3 Beatriz de Olaiz Navarro,4 Raquel Herrero,1,5 José Ángel Lorente,1,5,6 Ángel Cogolludo,1,2,3 Francisco Pérez-Vizcaíno,1,2,3 Laura Moreno1,2,3 ▸ Additional material is ABSTRACT published online only. To view Background Pulmonary hypertension (PH) is frequently Key messages please visit the journal online (http://dx.doi.org/10.1136/ observed in patients with acute respiratory distress thoraxjnl-2015-208067). syndrome (ARDS) and it is associated with an increased risk of mortality. Both acid sphingomyelinase (aSMase) 1Ciber Enfermedades What is the key question? Respiratorias (CIBERES), activity and interleukin 6 (IL-6) levels are increased in ▸ Pulmonary hypertension and right ventricular Madrid, Spain patients with sepsis and correlate with worst outcomes, dysfunction are prominent prognostic features 2 Department of Pharmacology, but their role in pulmonary vascular dysfunction of acute respiratory distress syndrome (ARDS) School of Medicine, pathogenesis has not yet been elucidated. Therefore, the which, given the unclear pathophysiology and Universidad Complutense de Madrid, Madrid, Spain aim of this study was to determine the potential the lack of approved pharmacological therapies, 3Gregorio Marañón Biomedical contribution of aSMase and IL-6 in the pulmonary demand the identification of new therapeutic Research Institution (IiSGM), vascular dysfunction induced by lipopolysaccharide (LPS).
    [Show full text]
  • Abcam Enzymatic Activity Assay Kits
    Less haste, more speed 用更快的速度，從容的完成實驗 我們擁有品項齊全的抗體、相關免疫實驗試劑，以及數百種偵測酵素活性的試劑 Signal transduction Metabolism 套組，協助研究者進行訊號傳遞 ( )、代謝 ( )、神經 Neuroscience Gene regulation Epigenetics 科學 ( )、基因調控 ( )、表觀遺傳 ( )、 Cancer Cardiovascular Oxidative stress 癌症 ( )、心血管 ( )、氧化壓力 ( ) 等相關研 瀏覽相關產品目錄 Cell culture Tissue lysate 究。 涵蓋樣本來源諸如：細胞培養 ( )、組織裂解物 ( ) 或體 Body fluid 液 ( ) 等 。 我們總是追求卓越，完整呈現給您最佳的抗體與分析試劑盒， 以協助您快速取得所需的實驗結果。 Abcam 各項特惠活動進行中，詳情請洽 台灣代理 ― 伯森生技。 酵素測定成功秘訣 Activity assay kits 活性測定試劑套組 ( ) Target/ Protein Detection method Cat. no. Target/ Protein Detection method Cat. no. Acetylcholinesterase Colorimetric ab138871 Aldo-Keto Reductase Colorimetric ab211112 Acetylcholinesterase Fluorescent ab138872 Aldolase Colorimetric ab196994 Acetylcholinesterase Colorimetric/ ab138873 Alkaline Phosphatase Colorimetric ab83369 Fluorometric Alkaline Phosphatase Fluorescent ab83371 Acetyltransferase Fluorescent ab204536 Alkaline Phosphatase Fluorescent ab138887 Acid Phosphatase Colorimetric ab83367 Alkaline Phosphatase Luminescent ab233466 Acid Phosphatase Fluorescent ab83370 Alkaline Sphingomyelinase Colorimetric ab241039 Acid Sphingomyelinase Colorimetric ab252889 Alpha Galactosidase Fluorescent ab239716 Acidic Sphingomyelinase Fluorescent ab190554 Alpha-Glucosidase Colorimetric ab174093 Aconitase Colorimetric ab83459 Alpha-Ketoglutarate Dehydrogenase Colorimetric ab185440 Aconitase Colorimetric ab109712 Amylase Colorimetric ab102523 Adenosine Deaminase Fluorescent ab204695 Arginase Colorimetric ab180877 Adenosine Deaminase Colorimetric ab211093 Asparaginase Colorimetric/
    [Show full text]
  • Structural Study of the Acid Sphingomyelinase Protein Family
    Structural Study of the Acid Sphingomyelinase Protein Family Alexei Gorelik Department of Biochemistry McGill University, Montreal August 2017 A thesis submitted to McGill University in partial fulfillment of the requirements of the degree of Doctor of Philosophy © Alexei Gorelik, 2017 Abstract The acid sphingomyelinase (ASMase) converts the lipid sphingomyelin (SM) to ceramide. This protein participates in lysosomal lipid metabolism and plays an additional role in signal transduction at the cell surface by cleaving the abundant SM to ceramide, thus modulating membrane properties. These functions are enabled by the enzyme’s lipid- and membrane- interacting saposin domain. ASMase is part of a small family along with the poorly characterized ASMase-like phosphodiesterases 3A and 3B (SMPDL3A,B). SMPDL3A does not hydrolyze SM but degrades extracellular nucleotides, and is potentially involved in purinergic signaling. SMPDL3B is a regulator of the innate immune response and podocyte function, and displays a partially defined lipid- and membrane-modifying activity. I carried out structural studies to gain insight into substrate recognition and molecular functions of the ASMase family of proteins. Crystal structures of SMPDL3A uncovered the helical fold of a novel C-terminal subdomain, a slightly distinct catalytic mechanism, and a nucleotide-binding mode without specific contacts to their nucleoside moiety. The ASMase investigation revealed a conformational flexibility of its saposin domain: this module can switch from a detached, closed conformation to an open form which establishes a hydrophobic interface to the catalytic domain. This open configuration represents the active form of the enzyme, likely allowing lipid access to the active site. The SMPDL3B structure showed a narrow, boot-shaped substrate binding site that accommodates the head group of SM.
    [Show full text]
  • Acid Sphingomyelinase Regulates the Localization and Trafficking of Palmitoylated Proteins
    Chemistry and Biochemistry Faculty Publications Chemistry and Biochemistry 5-29-2019 Acid Sphingomyelinase Regulates the Localization and Trafficking of Palmitoylated Proteins Xiahui Xiong University of Nevada, Las Vegas, [email protected] Chia-Fang Lee Protea Biosciences Wenjing Li University of Nevada, Las Vegas, [email protected] Jiekai Yu University of Nevada, Las Vegas, [email protected] Linyu Zhu University of Nevada, Las Vegas SeeFollow next this page and for additional additional works authors at: https:/ /digitalscholarship.unlv.edu/chem_fac_articles Part of the Biochemistry, Biophysics, and Structural Biology Commons Repository Citation Xiong, X., Lee, C., Li, W., Yu, J., Zhu, L., Kim, Y., Zhang, H., Sun, H. (2019). Acid Sphingomyelinase Regulates the Localization and Trafficking of Palmitoylated Proteins. Biology Open 1-56. Company of Biologists. http://dx.doi.org/10.1242/bio.040311 This Article is protected by copyright and/or related rights. It has been brought to you by Digital Scholarship@UNLV with permission from the rights-holder(s). You are free to use this Article in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s) directly, unless additional rights are indicated by a Creative Commons license in the record and/ or on the work itself. This Article has been accepted for inclusion in Chemistry and Biochemistry Faculty Publications by an authorized administrator of Digital Scholarship@UNLV. For
    [Show full text]
  • The Activity of Lysosomal Enzymes in Blood Serum, Liver, Kidney and Skeletal Muscle of Rabbits Divergently Selected for Locomotor Activity in Open-Field Test
    Animal Science Papers and Reports vol. 27 (2009) no. 3, 249-257 Institute of Genetics and Animal Breeding, Jastrzębiec, Poland REPORT The activity of lysosomal enzymes in blood serum, liver, kidney and skeletal muscle of rabbits divergently selected for locomotor activity in open-field test Artur Jóźwik*, Anna Śliwa-Jóźwik, Tadeusz Jezierski, Wojciech Daniewski, Aleksandra Górecka, Adam Kołątaj Polish Academy of Sciences Institute of Genetics and Animal Breeding, Jastrzębiec, 05-552 Wólka Kosowska, Poland (Received August 25, 2008; accepted March 10, 2009) Twenty males were used from generation 8 of rabbits divergently selected for high (line H, n=10) vs. low (line L, n=10) locomotor activity in the open-field (OF-test). At the age of 98 days, blood samples were withdrawn from the ear vein and the rabbits were killed. Immediately, liver, kidney and the left femoral muscle samples were excised. In lysosomal fractions of blood serum and three tissues mentioned the activity of lysosomal enzymes AlaAP, LeuAP, ArgAP, Cat D and L, AcP, EL, LAL, BGRD, BGAL, BGLU, aGlu, MAN and HEX was determined. Significant interline differences were identified in activity of blood and tissue enzymes in question. The results suggest that the divergent selection for high vs. low locomotor activity in the open-field (OF-test) alters the lysosomal degradation processes in the organism. KEY WORDS: lysosomal enzymes / open-field test / rabbits / selection *Corresponding author: [email protected] 249 A. Jóźwik et al. The metabolic processes in live cells and tissues depend, among others, on specific rate of synthesis and degradation of basic energetic compounds.
    [Show full text]
  • The Role of Lysosomal Acid Lipase in Regulation of the Atp
    THE ROLE OF LYSOSOMAL ACID LIPASE IN REGULATION OF THE ATP- BINDING CASSETTE TRANSPORTER A1, HIGH DENSITY LIPOPROTEIN AND REVERSE CHOLESTEROL TRANSPORT by Kristin Louise Bowden B.Sc., Queen’s University, 2005 M.Sc., Dalhousie University, 2008. A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY in THE FACULTY OF GRADUATE AND POSTDOCTORAL STUDIES (Experimental Medicine) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) October 2013 © Kristin Louise Bowden, 2013. Abstract The key regulator of initial HDL particle formation by cells is the ATP-binding cassette transporter A1 (ABCA1). ABCA1 expression is regulated primarily by oxysterol dependent activation of the liver X receptor (LXR). We investigated the role of lysosomal cholesterol on ABCA1 regulation by studying the lysosomal disorder Cholesteryl Ester Storage Disease (CESD). CESD is caused by genetic mutations in the LIP-A gene that result in only 5% of normal activity of lysosomal acid lipase (LAL), an enzyme that hydrolyzes cholesteryl esters (CE) and triglycerides on internalized lipoproteins specifically within the lysosome. We hypothesized that the flux of unesterified cholesterol out of the lysosomes from LAL- mediated hydrolysis of LDL cholesteryl esters is a key regulator of cellular ABCA1 expression, HDL formation and reverse cholesterol transport (RCT). We found that primary skin fibroblasts derived from individuals with CESD had impaired upregulation of ABCA1 in response to LDL loading, reduced phospholipid and cholesterol efflux to apoA-I, lower production of 27-hydroxycholesterol (27-OH) production in response to LDL loading and reduced α-HDL particle formation. This defect was recapitulated in normal fibroblasts following treatment with LAL inhibitors, whereas, treatment with conditioned medium from normal fibroblasts containing secreted LAL rescued ABCA1 expression, apoA-I-mediated cholesterol efflux, HDL particle formation and production of 27-OH by CESD cells.
    [Show full text]
  • The Physiological Role of Glucocorticoid and Mineralocorticoid Receptor Activation in Zebrafish
    University of Calgary PRISM: University of Calgary's Digital Repository Graduate Studies The Vault: Electronic Theses and Dissertations 2019-06-25 The Physiological Role of Glucocorticoid and Mineralocorticoid Receptor Activation in Zebrafish Faught, Leslie Erin Faught, L. E. (2019). The Physiological Role of Glucocorticoid and Mineralocorticoid Receptor Activation in Zebrafish (Unpublished doctoral thesis). University of Calgary, Calgary, AB. http://hdl.handle.net/1880/110575 doctoral thesis University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission. Downloaded from PRISM: https://prism.ucalgary.ca UNIVERSITY OF CALGARY The Physiological Role of Glucocorticoid and Mineralocorticoid Receptor Activation in Zebrafish by Leslie Erin Faught A THESIS SUBMITTED TO THE FACULTY OF GRADUATE STUDIES IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY GRADUATE PROGRAM IN BIOLOGICAL SCIENCES CALGARY, ALBERTA JUNE, 2019 © Leslie Erin Faught 2019 Abstract Glucocorticoids are key mediators of the vertebrate stress response. In teleosts, the primary glucocorticoid, cortisol, is a ligand for two corticosteroid receptors (CRs), the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR). The affinity of cortisol for these receptors is markedly different, with MR having an almost 10-fold higher affinity for the ligand compared to GR. This led to the hypothesis 30 years ago in mammals, that MR is responsible for basal cortisol function, while GR is active only when cortisol levels are high.
    [Show full text]
  • The Role of Lipid Metabolism in Aging, Lifespan Regulation, and Age‐Related Disease
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Loughborough University Institutional Repository Received: 6 May 2019 | Revised: 11 August 2019 | Accepted: 4 September 2019 DOI: 10.1111/acel.13048 REVIEW The role of lipid metabolism in aging, lifespan regulation, and age‐related disease Adiv A. Johnson1 | Alexandra Stolzing2,3 1Nikon Instruments, Melville, NY, USA Abstract 2BIOAGE Labs, Richmond, CA, USA 3Loughborough University, Loughborough, An emerging body of data suggests that lipid metabolism has an important role to UK play in the aging process. Indeed, a plethora of dietary, pharmacological, genetic, and Correspondence surgical lipid‐related interventions extend lifespan in nematodes, fruit flies, mice, and Adiv A. Johnson, Nikon Instruments, rats. For example, the impairment of genes involved in ceramide and sphingolipid Melville, NY, USA. Email: [email protected] synthesis extends lifespan in both worms and flies. The overexpression of fatty acid amide hydrolase or lysosomal lipase prolongs life in Caenorhabditis elegans, while the overexpression of diacylglycerol lipase enhances longevity in both C. elegans and Drosophila melanogaster. The surgical removal of adipose tissue extends lifespan in rats, and increased expression of apolipoprotein D enhances survival in both flies and mice. Mouse lifespan can be additionally extended by the genetic deletion of diacyl‐ glycerol acyltransferase 1, treatment with the steroid 17‐α‐estradiol, or a ketogenic diet. Moreover, deletion of the phospholipase A2 receptor improves various health‐ span parameters in a progeria mouse model. Genome‐wide association studies have found several lipid‐related variants to be associated with human aging. For example, the epsilon 2 and epsilon 4 alleles of apolipoprotein E are associated with extreme longevity and late‐onset neurodegenerative disease, respectively.
    [Show full text]