Abnormal activity of membrane phospholipid synthetic enzymes in the brain of patients with Friedreich's ataxia and spinocerebellar atrophy type‐1
Identifieur interne : 000F10 ( Istex/Corpus ); précédent : 000F09; suivant : 000F11Abnormal activity of membrane phospholipid synthetic enzymes in the brain of patients with Friedreich's ataxia and spinocerebellar atrophy type‐1
Auteurs : Brian M. Ross ; Klaus Eder ; Anna Moszczynska ; Nikolaos Mamalias ; Jacques Lamarche ; Lee Ang ; Massimo Pandolfo ; Guy Rouleau ; Manfred Kirchgessner ; Stephen J. KishSource :
- Movement Disorders [ 0885-3185 ] ; 2000-03.
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- KwdEn :
Abstract
Much evidence, derived from biochemical studies of both blood and autopsied brain, has suggested that phospholipid metabolism is abnormal in patients with Friedreich's ataxia (FA), a disorder characterized by severe neuronal loss in the spinal cord and lower brain stem with no, or only modest, damage in other brain regions. To establish the cause of our recent finding of reduced brain levels of phospholipids in FA, we assayed activities of 10 phospholipid‐metabolizing enzymes in the autopsied cerebellar cortex of patients with the disorder and, for comparison, in a group of patients with spinocerebellar ataxia type 1 (SCA‐1), a disease characterized, unlike FA, by marked neuronal loss in the cerebellar cortex. Enzyme activities were also measured in four brain areas which are relatively unaffected morphologically in both FA and SCA‐1. We found that ethanolamine kinase activity was increased in multiple brain regions of patients with FA (increased 31%–137%) and, more modestly, in SCA‐1 (increased 39%–60%), suggesting a nonspecific enhancement of phosphoethanolamine production in both disorders. In contrast, the activity of phosphoethanolamine cytidylyltransferase (PECT), the rate‐limiting enzyme of phosphatidylethanolamine synthesis, was significantly and markedly decreased by 35%–78% in the cerebellar, frontal, and occipital cortices of patients with FA but was normal in SCA‐1. Reduced PECT activity in FA may explain the lower brain levels of phosphatidylethanolamine in the disorder. Moreover, because decreased PECT activity in FA occurs in brain regions having no, or only modest, morphologic damage, this may represent a systemic change consequent to the frataxin gene defect. Our data also suggest that therapeutic intervention in FA designed to increase synthesis of membrane phospholipids may warrant further investigation.
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DOI: 10.1002/1531-8257(200003)15:2<294::AID-MDS1013>3.0.CO;2-D
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Ross</name><affiliation><mods:affiliation>Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada</mods:affiliation></affiliation></author><author><name sortKey="Eder, Klaus" sort="Eder, Klaus" uniqKey="Eder K" first="Klaus" last="Eder">Klaus Eder</name><affiliation><mods:affiliation>Institute of Nutrition Physiology, Technical University of Munich, Munich, Germany</mods:affiliation></affiliation></author><author><name sortKey="Moszczynska, Anna" sort="Moszczynska, Anna" uniqKey="Moszczynska A" first="Anna" last="Moszczynska">Anna Moszczynska</name><affiliation><mods:affiliation>Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada</mods:affiliation></affiliation></author><author><name sortKey="Mamalias, Nikolaos" sort="Mamalias, Nikolaos" uniqKey="Mamalias N" first="Nikolaos" last="Mamalias">Nikolaos Mamalias</name><affiliation><mods:affiliation>Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada</mods:affiliation></affiliation></author><author><name sortKey="Lamarche, Jacques" sort="Lamarche, Jacques" uniqKey="Lamarche J" first="Jacques" last="Lamarche">Jacques Lamarche</name><affiliation><mods:affiliation>Centre Universitaire de Santé de l'Estrie, Sherbrooke, Quebec, Canada</mods:affiliation></affiliation></author><author><name sortKey="Ang, Lee" sort="Ang, Lee" uniqKey="Ang L" first="Lee" last="Ang">Lee Ang</name><affiliation><mods:affiliation>Sunnybrook Health Science Centre, Toronto, Ontario, Canada</mods:affiliation></affiliation></author><author><name sortKey="Pandolfo, Massimo" sort="Pandolfo, Massimo" uniqKey="Pandolfo M" first="Massimo" last="Pandolfo">Massimo Pandolfo</name><affiliation><mods:affiliation>Centre Hospitalier de l' Université de Montréal</mods:affiliation></affiliation></author><author><name sortKey="Rouleau, Guy" sort="Rouleau, Guy" uniqKey="Rouleau G" first="Guy" last="Rouleau">Guy Rouleau</name><affiliation><mods:affiliation>Montreal General Hospital Research Institute, Montreal, Quebec, Canada</mods:affiliation></affiliation></author><author><name sortKey="Kirchgessner, Manfred" sort="Kirchgessner, Manfred" uniqKey="Kirchgessner M" first="Manfred" last="Kirchgessner">Manfred Kirchgessner</name><affiliation><mods:affiliation>Institute of Nutrition Physiology, Technical University of Munich, Munich, Germany</mods:affiliation></affiliation></author><author><name sortKey="Kish, Stephen J" sort="Kish, Stephen J" uniqKey="Kish S" first="Stephen J." last="Kish">Stephen J. Kish</name><affiliation><mods:affiliation>Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Movement Disorders</title><title level="j" type="sub">Official Journal of the Movement Disorder Society</title><title level="j" type="abbrev">Mov. 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To establish the cause of our recent finding of reduced brain levels of phospholipids in FA, we assayed activities of 10 phospholipid‐metabolizing enzymes in the autopsied cerebellar cortex of patients with the disorder and, for comparison, in a group of patients with spinocerebellar ataxia type 1 (SCA‐1), a disease characterized, unlike FA, by marked neuronal loss in the cerebellar cortex. Enzyme activities were also measured in four brain areas which are relatively unaffected morphologically in both FA and SCA‐1. We found that ethanolamine kinase activity was increased in multiple brain regions of patients with FA (increased 31%–137%) and, more modestly, in SCA‐1 (increased 39%–60%), suggesting a nonspecific enhancement of phosphoethanolamine production in both disorders. In contrast, the activity of phosphoethanolamine cytidylyltransferase (PECT), the rate‐limiting enzyme of phosphatidylethanolamine synthesis, was significantly and markedly decreased by 35%–78% in the cerebellar, frontal, and occipital cortices of patients with FA but was normal in SCA‐1. Reduced PECT activity in FA may explain the lower brain levels of phosphatidylethanolamine in the disorder. Moreover, because decreased PECT activity in FA occurs in brain regions having no, or only modest, morphologic damage, this may represent a systemic change consequent to the frataxin gene defect. Our data also suggest that therapeutic intervention in FA designed to increase synthesis of membrane phospholipids may warrant further investigation.</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Brian M. Ross PhD</name><affiliations><json:string>Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada</json:string><json:string>Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada</json:string></affiliations></json:item><json:item><name>Klaus Eder PhD</name><affiliations><json:string>Institute of Nutrition Physiology, Technical University of Munich, Munich, Germany</json:string></affiliations></json:item><json:item><name>Anna Moszczynska MSc</name><affiliations><json:string>Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada</json:string></affiliations></json:item><json:item><name>Nikolaos Mamalias BSc</name><affiliations><json:string>Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada</json:string></affiliations></json:item><json:item><name>Jacques Lamarche MD</name><affiliations><json:string>Centre Universitaire de Santé de l'Estrie, Sherbrooke, Quebec, Canada</json:string></affiliations></json:item><json:item><name>Lee Ang MD</name><affiliations><json:string>Sunnybrook Health Science Centre, Toronto, Ontario, Canada</json:string></affiliations></json:item><json:item><name>Massimo Pandolfo MD</name><affiliations><json:string>Centre Hospitalier de l' Université de Montréal</json:string></affiliations></json:item><json:item><name>Guy Rouleau MD, PhD</name><affiliations><json:string>Montreal General Hospital Research Institute, Montreal, Quebec, Canada</json:string></affiliations></json:item><json:item><name>Manfred Kirchgessner MD, PhD</name><affiliations><json:string>Institute of Nutrition Physiology, Technical University of Munich, Munich, Germany</json:string></affiliations></json:item><json:item><name>Stephen J. Kish PhD</name><affiliations><json:string>Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada</json:string><json:string>Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>Membrane</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Phosphatidylethanolamine</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Phosphoethanolamine cytidylyltransferase</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Ethanolamine kinase</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Cerebellar cortex</value></json:item></subject><language><json:string>eng</json:string></language><abstract>Much evidence, derived from biochemical studies of both blood and autopsied brain, has suggested that phospholipid metabolism is abnormal in patients with Friedreich's ataxia (FA), a disorder characterized by severe neuronal loss in the spinal cord and lower brain stem with no, or only modest, damage in other brain regions. To establish the cause of our recent finding of reduced brain levels of phospholipids in FA, we assayed activities of 10 phospholipid‐metabolizing enzymes in the autopsied cerebellar cortex of patients with the disorder and, for comparison, in a group of patients with spinocerebellar ataxia type 1 (SCA‐1), a disease characterized, unlike FA, by marked neuronal loss in the cerebellar cortex. Enzyme activities were also measured in four brain areas which are relatively unaffected morphologically in both FA and SCA‐1. We found that ethanolamine kinase activity was increased in multiple brain regions of patients with FA (increased 31%–137%) and, more modestly, in SCA‐1 (increased 39%–60%), suggesting a nonspecific enhancement of phosphoethanolamine production in both disorders. In contrast, the activity of phosphoethanolamine cytidylyltransferase (PECT), the rate‐limiting enzyme of phosphatidylethanolamine synthesis, was significantly and markedly decreased by 35%–78% in the cerebellar, frontal, and occipital cortices of patients with FA but was normal in SCA‐1. Reduced PECT activity in FA may explain the lower brain levels of phosphatidylethanolamine in the disorder. Moreover, because decreased PECT activity in FA occurs in brain regions having no, or only modest, morphologic damage, this may represent a systemic change consequent to the frataxin gene defect. 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No. #26034;</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Abnormal activity of membrane phospholipid synthetic enzymes in the brain of patients with Friedreich's ataxia and spinocerebellar atrophy type‐1</title><author><persName><forename type="first">Brian M.</forename><surname>Ross</surname><roleName type="degree">PhD</roleName></persName><note type="correspondence"><p>Correspondence: Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, Canada M5T 1R8</p></note><affiliation>Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada</affiliation><affiliation>Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada</affiliation></author><author><persName><forename type="first">Klaus</forename><surname>Eder</surname><roleName type="degree">PhD</roleName></persName><affiliation>Institute of Nutrition Physiology, Technical University of Munich, Munich, Germany</affiliation></author><author><persName><forename type="first">Anna</forename><surname>Moszczynska</surname><roleName type="degree">MSc</roleName></persName><affiliation>Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada</affiliation></author><author><persName><forename type="first">Nikolaos</forename><surname>Mamalias</surname><roleName type="degree">BSc</roleName></persName><affiliation>Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada</affiliation></author><author><persName><forename type="first">Jacques</forename><surname>Lamarche</surname><roleName type="degree">MD</roleName></persName><affiliation>Centre Universitaire de Santé de l'Estrie, Sherbrooke, Quebec, Canada</affiliation></author><author><persName><forename type="first">Lee</forename><surname>Ang</surname><roleName type="degree">MD</roleName></persName><affiliation>Sunnybrook Health Science Centre, Toronto, Ontario, Canada</affiliation></author><author><persName><forename type="first">Massimo</forename><surname>Pandolfo</surname><roleName type="degree">MD</roleName></persName><affiliation>Centre Hospitalier de l' Université de Montréal</affiliation></author><author><persName><forename type="first">Guy</forename><surname>Rouleau</surname><roleName type="degree">MD, PhD</roleName></persName><affiliation>Montreal General Hospital Research Institute, Montreal, Quebec, Canada</affiliation></author><author><persName><forename type="first">Manfred</forename><surname>Kirchgessner</surname><roleName type="degree">MD, PhD</roleName></persName><affiliation>Institute of Nutrition Physiology, Technical University of Munich, Munich, Germany</affiliation></author><author><persName><forename type="first">Stephen J.</forename><surname>Kish</surname><roleName type="degree">PhD</roleName></persName><affiliation>Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada</affiliation><affiliation>Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada</affiliation></author></analytic><monogr><title level="j">Movement Disorders</title><title level="j" type="sub">Official Journal of the Movement Disorder Society</title><title level="j" type="abbrev">Mov. Disord.</title><idno type="pISSN">0885-3185</idno><idno type="eISSN">1531-8257</idno><idno type="DOI">10.1002/(ISSN)1531-8257</idno><imprint><publisher>John Wiley & Sons, Inc.</publisher><pubPlace>New York</pubPlace><date type="published" when="2000-03"></date><biblScope unit="vol">15</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="294">294</biblScope><biblScope unit="page" to="300">300</biblScope></imprint></monogr><idno type="istex">498308B9FD34DE4E58068FB7F2112415E3F46725</idno><idno type="DOI">10.1002/1531-8257(200003)15:2<294::AID-MDS1013>3.0.CO;2-D</idno><idno type="ArticleID">MDS1013</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2000</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Much evidence, derived from biochemical studies of both blood and autopsied brain, has suggested that phospholipid metabolism is abnormal in patients with Friedreich's ataxia (FA), a disorder characterized by severe neuronal loss in the spinal cord and lower brain stem with no, or only modest, damage in other brain regions. To establish the cause of our recent finding of reduced brain levels of phospholipids in FA, we assayed activities of 10 phospholipid‐metabolizing enzymes in the autopsied cerebellar cortex of patients with the disorder and, for comparison, in a group of patients with spinocerebellar ataxia type 1 (SCA‐1), a disease characterized, unlike FA, by marked neuronal loss in the cerebellar cortex. Enzyme activities were also measured in four brain areas which are relatively unaffected morphologically in both FA and SCA‐1. We found that ethanolamine kinase activity was increased in multiple brain regions of patients with FA (increased 31%–137%) and, more modestly, in SCA‐1 (increased 39%–60%), suggesting a nonspecific enhancement of phosphoethanolamine production in both disorders. In contrast, the activity of phosphoethanolamine cytidylyltransferase (PECT), the rate‐limiting enzyme of phosphatidylethanolamine synthesis, was significantly and markedly decreased by 35%–78% in the cerebellar, frontal, and occipital cortices of patients with FA but was normal in SCA‐1. Reduced PECT activity in FA may explain the lower brain levels of phosphatidylethanolamine in the disorder. Moreover, because decreased PECT activity in FA occurs in brain regions having no, or only modest, morphologic damage, this may represent a systemic change consequent to the frataxin gene defect. Our data also suggest that therapeutic intervention in FA designed to increase synthesis of membrane phospholipids may warrant further investigation.</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head><item><term>Membrane</term></item><item><term>Phosphatidylethanolamine</term></item><item><term>Phosphoethanolamine cytidylyltransferase</term></item><item><term>Ethanolamine kinase</term></item><item><term>Cerebellar cortex</term></item></list></keywords></textClass><textClass><keywords scheme="Journal Subject"><list><head>Article category</head><item><term>Article</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="1999-05-27">Received</change><change when="1999-12-22">Registration</change><change when="2000-03">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/498308B9FD34DE4E58068FB7F2112415E3F46725/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Wiley, elements deleted: body"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="yes"</istex:xmlDeclaration><istex:document><component version="2.0" type="serialArticle" xml:lang="en"><header><publicationMeta level="product"><publisherInfo><publisherName>John Wiley & Sons, Inc.</publisherName><publisherLoc>New York</publisherLoc></publisherInfo><doi registered="yes">10.1002/(ISSN)1531-8257</doi><issn type="print">0885-3185</issn><issn type="electronic">1531-8257</issn><idGroup><id type="product" value="MDS"></id></idGroup><titleGroup><title type="main" xml:lang="en" sort="MOVEMENT DISORDERS">Movement Disorders</title><title type="subtitle">Official Journal of the Movement Disorder Society</title><title type="short">Mov. 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date="1999-11-29"></event><event type="manuscriptAccepted" date="1999-12-22"></event><event type="firstOnline" date="2001-01-31"></event><event type="publishedOnlineFinalForm" date="2001-01-31"></event><event type="xmlConverted" agent="Converter:JWSART34_TO_WML3G version:2.3.6 mode:FullText source:HeaderRef result:HeaderRef" date="2010-04-20"></event><event type="xmlConverted" agent="Converter:WILEY_ML3G_TO_WILEY_ML3GV2 version:3.8.8" date="2014-02-02"></event><event type="xmlConverted" agent="Converter:WML3G_To_WML3G version:4.1.7 mode:FullText,remove_FC" date="2014-11-01"></event></eventGroup><numberingGroup><numbering type="pageFirst">294</numbering><numbering type="pageLast">300</numbering></numberingGroup><correspondenceTo>Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, Canada M5T 1R8</correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:MDS.MDS1013.pdf"></link></linkGroup></publicationMeta><contentMeta><countGroup><count type="figureTotal" number="4"></count><count type="tableTotal" number="0"></count><count type="referenceTotal" number="26"></count><count type="wordTotal" number="3591"></count></countGroup><titleGroup><title type="main" xml:lang="en">Abnormal activity of membrane phospholipid synthetic enzymes in the brain of patients with Friedreich's ataxia and spinocerebellar atrophy type‐1</title><title type="short" xml:lang="en">Phospholipid Metabolizing Enzymes in Ataxia</title></titleGroup><creators><creator xml:id="au1" creatorRole="author" affiliationRef="#af1 #af2" corresponding="yes"><personName><givenNames>Brian M.</givenNames><familyName>Ross</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au2" creatorRole="author" affiliationRef="#af3"><personName><givenNames>Klaus</givenNames><familyName>Eder</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au3" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Anna</givenNames><familyName>Moszczynska</familyName><degrees>MSc</degrees></personName></creator><creator xml:id="au4" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Nikolaos</givenNames><familyName>Mamalias</familyName><degrees>BSc</degrees></personName></creator><creator xml:id="au5" creatorRole="author" affiliationRef="#af4"><personName><givenNames>Jacques</givenNames><familyName>Lamarche</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au6" creatorRole="author" affiliationRef="#af5"><personName><givenNames>Lee</givenNames><familyName>Ang</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au7" creatorRole="author" affiliationRef="#af6"><personName><givenNames>Massimo</givenNames><familyName>Pandolfo</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au8" creatorRole="author" affiliationRef="#af7"><personName><givenNames>Guy</givenNames><familyName>Rouleau</familyName><degrees>MD, PhD</degrees></personName></creator><creator xml:id="au9" creatorRole="author" affiliationRef="#af3"><personName><givenNames>Manfred</givenNames><familyName>Kirchgessner</familyName><degrees>MD, PhD</degrees></personName></creator><creator xml:id="au10" creatorRole="author" affiliationRef="#af1 #af2"><personName><givenNames>Stephen J.</givenNames><familyName>Kish</familyName><degrees>PhD</degrees></personName></creator></creators><affiliationGroup><affiliation xml:id="af1" countryCode="CA" type="organization"><unparsedAffiliation>Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada</unparsedAffiliation></affiliation><affiliation xml:id="af2" countryCode="CA" type="organization"><unparsedAffiliation>Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada</unparsedAffiliation></affiliation><affiliation xml:id="af3" countryCode="DE" type="organization"><unparsedAffiliation>Institute of Nutrition Physiology, Technical University of Munich, Munich, Germany</unparsedAffiliation></affiliation><affiliation xml:id="af4" countryCode="CA" type="organization"><unparsedAffiliation>Centre Universitaire de Santé de l'Estrie, Sherbrooke, Quebec, Canada</unparsedAffiliation></affiliation><affiliation xml:id="af5" countryCode="CA" type="organization"><unparsedAffiliation>Sunnybrook Health Science Centre, Toronto, Ontario, Canada</unparsedAffiliation></affiliation><affiliation xml:id="af6" countryCode="CA" type="organization"><unparsedAffiliation>Centre Hospitalier de l' Université de Montréal</unparsedAffiliation></affiliation><affiliation xml:id="af7" countryCode="CA" type="organization"><unparsedAffiliation>Montreal General Hospital Research Institute, Montreal, Quebec, Canada</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en" type="author"><keyword xml:id="kwd1">Membrane</keyword><keyword xml:id="kwd2">Phosphatidylethanolamine</keyword><keyword xml:id="kwd3">Phosphoethanolamine cytidylyltransferase</keyword><keyword xml:id="kwd4">Ethanolamine kinase</keyword><keyword xml:id="kwd5">Cerebellar cortex</keyword></keywordGroup><fundingInfo><fundingAgency>US NINDS</fundingAgency><fundingNumber>#26034</fundingNumber></fundingInfo><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><p>Much evidence, derived from biochemical studies of both blood and autopsied brain, has suggested that phospholipid metabolism is abnormal in patients with Friedreich's ataxia (FA), a disorder characterized by severe neuronal loss in the spinal cord and lower brain stem with no, or only modest, damage in other brain regions. To establish the cause of our recent finding of reduced brain levels of phospholipids in FA, we assayed activities of 10 phospholipid‐metabolizing enzymes in the autopsied cerebellar cortex of patients with the disorder and, for comparison, in a group of patients with spinocerebellar ataxia type 1 (SCA‐1), a disease characterized, unlike FA, by marked neuronal loss in the cerebellar cortex. Enzyme activities were also measured in four brain areas which are relatively unaffected morphologically in both FA and SCA‐1. We found that ethanolamine kinase activity was increased in multiple brain regions of patients with FA (increased 31%–137%) and, more modestly, in SCA‐1 (increased 39%–60%), suggesting a nonspecific enhancement of phosphoethanolamine production in both disorders. In contrast, the activity of phosphoethanolamine cytidylyltransferase (PECT), the rate‐limiting enzyme of phosphatidylethanolamine synthesis, was significantly and markedly decreased by 35%–78% in the cerebellar, frontal, and occipital cortices of patients with FA but was normal in SCA‐1. Reduced PECT activity in FA may explain the lower brain levels of phosphatidylethanolamine in the disorder. Moreover, because decreased PECT activity in FA occurs in brain regions having no, or only modest, morphologic damage, this may represent a systemic change consequent to the frataxin gene defect. Our data also suggest that therapeutic intervention in FA designed to increase synthesis of membrane phospholipids may warrant further investigation.</p></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><!--Version 0.6 générée le 4-12-2015--><mods version="3.6"><titleInfo lang="en"><title>Abnormal activity of membrane phospholipid synthetic enzymes in the brain of patients with Friedreich's ataxia and spinocerebellar atrophy type‐1</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>Phospholipid Metabolizing Enzymes in Ataxia</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Abnormal activity of membrane phospholipid synthetic enzymes in the brain of patients with Friedreich's ataxia and spinocerebellar atrophy type‐1</title></titleInfo><name type="personal"><namePart type="given">Brian M.</namePart><namePart type="family">Ross</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada</affiliation><affiliation>Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada</affiliation><description>Correspondence: Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, Canada M5T 1R8</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Klaus</namePart><namePart type="family">Eder</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Institute of Nutrition Physiology, Technical University of Munich, Munich, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Anna</namePart><namePart type="family">Moszczynska</namePart><namePart type="termsOfAddress">MSc</namePart><affiliation>Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Nikolaos</namePart><namePart type="family">Mamalias</namePart><namePart type="termsOfAddress">BSc</namePart><affiliation>Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jacques</namePart><namePart type="family">Lamarche</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Centre Universitaire de Santé de l'Estrie, Sherbrooke, Quebec, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Lee</namePart><namePart type="family">Ang</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Sunnybrook Health Science Centre, Toronto, Ontario, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Massimo</namePart><namePart type="family">Pandolfo</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Centre Hospitalier de l' Université de Montréal</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Guy</namePart><namePart type="family">Rouleau</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Montreal General Hospital Research Institute, Montreal, Quebec, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Manfred</namePart><namePart type="family">Kirchgessner</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Institute of Nutrition Physiology, Technical University of Munich, Munich, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Stephen J.</namePart><namePart type="family">Kish</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada</affiliation><affiliation>Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre authority="originalCategForm">article</genre><originInfo><publisher>John Wiley & Sons, Inc.</publisher><place><placeTerm type="text">New York</placeTerm></place><dateIssued encoding="w3cdtf">2000-03</dateIssued><dateCaptured encoding="w3cdtf">1999-05-27</dateCaptured><dateValid encoding="w3cdtf">1999-12-22</dateValid><copyrightDate encoding="w3cdtf">2000</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType><extent unit="figures">4</extent><extent unit="references">26</extent><extent unit="words">3591</extent></physicalDescription><abstract lang="en">Much evidence, derived from biochemical studies of both blood and autopsied brain, has suggested that phospholipid metabolism is abnormal in patients with Friedreich's ataxia (FA), a disorder characterized by severe neuronal loss in the spinal cord and lower brain stem with no, or only modest, damage in other brain regions. To establish the cause of our recent finding of reduced brain levels of phospholipids in FA, we assayed activities of 10 phospholipid‐metabolizing enzymes in the autopsied cerebellar cortex of patients with the disorder and, for comparison, in a group of patients with spinocerebellar ataxia type 1 (SCA‐1), a disease characterized, unlike FA, by marked neuronal loss in the cerebellar cortex. Enzyme activities were also measured in four brain areas which are relatively unaffected morphologically in both FA and SCA‐1. We found that ethanolamine kinase activity was increased in multiple brain regions of patients with FA (increased 31%–137%) and, more modestly, in SCA‐1 (increased 39%–60%), suggesting a nonspecific enhancement of phosphoethanolamine production in both disorders. In contrast, the activity of phosphoethanolamine cytidylyltransferase (PECT), the rate‐limiting enzyme of phosphatidylethanolamine synthesis, was significantly and markedly decreased by 35%–78% in the cerebellar, frontal, and occipital cortices of patients with FA but was normal in SCA‐1. Reduced PECT activity in FA may explain the lower brain levels of phosphatidylethanolamine in the disorder. Moreover, because decreased PECT activity in FA occurs in brain regions having no, or only modest, morphologic damage, this may represent a systemic change consequent to the frataxin gene defect. Our data also suggest that therapeutic intervention in FA designed to increase synthesis of membrane phospholipids may warrant further investigation.</abstract><note type="funding">US NINDS - No. #26034; </note><subject lang="en"><genre>Keywords</genre><topic>Membrane</topic><topic>Phosphatidylethanolamine</topic><topic>Phosphoethanolamine cytidylyltransferase</topic><topic>Ethanolamine kinase</topic><topic>Cerebellar cortex</topic></subject><relatedItem type="host"><titleInfo><title>Movement Disorders</title><subTitle>Official Journal of the Movement Disorder Society</subTitle></titleInfo><titleInfo type="abbreviated"><title>Mov. Disord.</title></titleInfo><subject><genre>article category</genre><topic>Article</topic></subject><identifier type="ISSN">0885-3185</identifier><identifier type="eISSN">1531-8257</identifier><identifier type="DOI">10.1002/(ISSN)1531-8257</identifier><identifier type="PublisherID">MDS</identifier><part><date>2000</date><detail type="volume"><caption>vol.</caption><number>15</number></detail><detail type="issue"><caption>no.</caption><number>2</number></detail><extent unit="pages"><start>294</start><end>300</end><total>7</total></extent></part></relatedItem><identifier type="istex">498308B9FD34DE4E58068FB7F2112415E3F46725</identifier><identifier type="DOI">10.1002/1531-8257(200003)15:2<294::AID-MDS1013>3.0.CO;2-D</identifier><identifier type="ArticleID">MDS1013</identifier><accessCondition type="use and reproduction" contentType="copyright">Copyright © 2000 Movement Disorder Society</accessCondition><recordInfo><recordOrigin>John Wiley & Sons, Inc.</recordOrigin><recordContentSource>WILEY</recordContentSource></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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