Abnormal activity of membrane phospholipid synthetic enzymes in the brain of patients with Friedreich's ataxia and spinocerebellar atrophy type‐1
Identifieur interne : 004B63 ( Main/Exploration ); précédent : 004B62; suivant : 004B64Abnormal activity of membrane phospholipid synthetic enzymes in the brain of patients with Friedreich's ataxia and spinocerebellar atrophy type‐1
Auteurs : Brian M. Ross [Canada] ; Klaus Eder [Allemagne] ; Anna Moszczynska [Canada] ; Nikolaos Mamalias [Canada] ; Jacques Lamarche [Canada] ; Lee Ang [Canada] ; Massimo Pandolfo ; Guy Rouleau [Canada] ; Manfred Kirchgessner [Allemagne] ; Stephen J. Kish [Canada]Source :
- Movement Disorders [ 0885-3185 ] ; 2000-03.
Descripteurs français
- Pascal (Inist)
- Wicri :
- topic : Homme.
English descriptors
- KwdEn :
- Adult, Brain (enzymology), Brain (pathology), Brain Mapping, Cerebellar Cortex (enzymology), Cerebellar Cortex (pathology), Cerebellar cortex, Cerebral Cortex (enzymology), Cerebral Cortex (pathology), Comparative study, Enzymatic activity, Ethanolamine kinase, Ethanolamine-phosphate cytidylytransferase, Exploration, Female, Friedreich Ataxia (diagnosis), Friedreich Ataxia (enzymology), Friedreich Ataxia (pathology), Friedreich ataxia, Human, Humans, Male, Membrane, Membrane Lipids (metabolism), Metabolism, Phosphatidylethanolamine, Phosphatidylethanolamines (metabolism), Phosphoethanolamine cytidylyltransferase, Phospholipid, Phospholipids (metabolism), Phosphotransferases (Alcohol Group Acceptor) (metabolism), Plasma membrane, Reference Values, Spinocerebellar Ataxias (diagnosis), Spinocerebellar Ataxias (enzymology), Spinocerebellar Ataxias (pathology), Spinocerebellar ataxia.
- MESH :
- chemical , metabolism : Membrane Lipids, Phosphatidylethanolamines, Phospholipids, Phosphotransferases (Alcohol Group Acceptor).
- diagnosis : Friedreich Ataxia, Spinocerebellar Ataxias.
- enzymology : Brain, Cerebellar Cortex, Cerebral Cortex, Friedreich Ataxia, Spinocerebellar Ataxias.
- pathology : Brain, Cerebellar Cortex, Cerebral Cortex, Friedreich Ataxia, Spinocerebellar Ataxias.
- Adult, Brain Mapping, Female, Humans, Male, Reference Values.
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.
Url:
DOI: 10.1002/1531-8257(200003)15:2<294::AID-MDS1013>3.0.CO;2-D
Affiliations:
- Allemagne, Canada
- Bavière, District de Haute-Bavière, Ontario
- Munich, Toronto
- Université Louis-et-Maximilien de Munich, Université de Toronto
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Le document en format XML
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Ross</name><affiliation wicri:level="4"><country xml:lang="fr">Canada</country><wicri:regionArea>Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation><affiliation wicri:level="4"><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Psychiatry, University of Toronto, Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Eder, Klaus" sort="Eder, Klaus" uniqKey="Eder K" first="Klaus" last="Eder">Klaus Eder</name><affiliation wicri:level="4"><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Nutrition Physiology, Technical University of Munich, Munich</wicri:regionArea><placeName><region type="land" nuts="1">Bavière</region><region type="district" nuts="2">District de Haute-Bavière</region><settlement type="city">Munich</settlement></placeName><orgName type="university">Université Louis-et-Maximilien de Munich</orgName></affiliation></author><author><name sortKey="Moszczynska, Anna" sort="Moszczynska, Anna" uniqKey="Moszczynska A" first="Anna" last="Moszczynska">Anna Moszczynska</name><affiliation wicri:level="4"><country xml:lang="fr">Canada</country><wicri:regionArea>Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Mamalias, Nikolaos" sort="Mamalias, Nikolaos" uniqKey="Mamalias N" first="Nikolaos" last="Mamalias">Nikolaos Mamalias</name><affiliation wicri:level="4"><country xml:lang="fr">Canada</country><wicri:regionArea>Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Lamarche, Jacques" sort="Lamarche, Jacques" uniqKey="Lamarche J" first="Jacques" last="Lamarche">Jacques Lamarche</name><affiliation wicri:level="1"><country xml:lang="fr">Canada</country><wicri:regionArea>Centre Universitaire de Santé de l'Estrie, Sherbrooke, Quebec</wicri:regionArea><wicri:noRegion>Quebec</wicri:noRegion></affiliation></author><author><name sortKey="Ang, Lee" sort="Ang, Lee" uniqKey="Ang L" first="Lee" last="Ang">Lee Ang</name><affiliation wicri:level="1"><country xml:lang="fr">Canada</country><wicri:regionArea>Sunnybrook Health Science Centre, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation></author><author><name sortKey="Pandolfo, Massimo" sort="Pandolfo, Massimo" uniqKey="Pandolfo M" first="Massimo" last="Pandolfo">Massimo Pandolfo</name><affiliation><wicri:noCountry code="no comma">Centre Hospitalier de l' Université de Montréal</wicri:noCountry></affiliation></author><author><name sortKey="Rouleau, Guy" sort="Rouleau, Guy" uniqKey="Rouleau G" first="Guy" last="Rouleau">Guy Rouleau</name><affiliation wicri:level="1"><country xml:lang="fr">Canada</country><wicri:regionArea>Montreal General Hospital Research Institute, Montreal, Quebec</wicri:regionArea><wicri:noRegion>Quebec</wicri:noRegion></affiliation></author><author><name sortKey="Kirchgessner, Manfred" sort="Kirchgessner, Manfred" uniqKey="Kirchgessner M" first="Manfred" last="Kirchgessner">Manfred Kirchgessner</name><affiliation wicri:level="4"><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Nutrition Physiology, Technical University of Munich, Munich</wicri:regionArea><placeName><region type="land" nuts="1">Bavière</region><region type="district" nuts="2">District de Haute-Bavière</region><settlement type="city">Munich</settlement></placeName><orgName type="university">Université Louis-et-Maximilien de Munich</orgName></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 wicri:level="4"><country xml:lang="fr">Canada</country><wicri:regionArea>Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation><affiliation wicri:level="4"><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Psychiatry, University of Toronto, Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></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. Disord.</title><idno type="ISSN">0885-3185</idno><idno type="eISSN">1531-8257</idno><imprint><publisher>John Wiley & Sons, Inc.</publisher><pubPlace>New York</pubPlace><date type="published" when="2000-03">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><idno type="ISSN">0885-3185</idno></series><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><seriesStmt><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term><term>Brain (enzymology)</term><term>Brain (pathology)</term><term>Brain Mapping</term><term>Cerebellar Cortex (enzymology)</term><term>Cerebellar Cortex (pathology)</term><term>Cerebellar cortex</term><term>Cerebral Cortex (enzymology)</term><term>Cerebral Cortex (pathology)</term><term>Comparative study</term><term>Enzymatic activity</term><term>Ethanolamine kinase</term><term>Ethanolamine-phosphate cytidylytransferase</term><term>Exploration</term><term>Female</term><term>Friedreich Ataxia (diagnosis)</term><term>Friedreich Ataxia (enzymology)</term><term>Friedreich Ataxia (pathology)</term><term>Friedreich ataxia</term><term>Human</term><term>Humans</term><term>Male</term><term>Membrane</term><term>Membrane Lipids (metabolism)</term><term>Metabolism</term><term>Phosphatidylethanolamine</term><term>Phosphatidylethanolamines (metabolism)</term><term>Phosphoethanolamine cytidylyltransferase</term><term>Phospholipid</term><term>Phospholipids (metabolism)</term><term>Phosphotransferases (Alcohol Group Acceptor) (metabolism)</term><term>Plasma membrane</term><term>Reference Values</term><term>Spinocerebellar Ataxias (diagnosis)</term><term>Spinocerebellar Ataxias (enzymology)</term><term>Spinocerebellar Ataxias (pathology)</term><term>Spinocerebellar ataxia</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Membrane Lipids</term><term>Phosphatidylethanolamines</term><term>Phospholipids</term><term>Phosphotransferases (Alcohol Group Acceptor)</term></keywords><keywords scheme="MESH" qualifier="diagnosis" xml:lang="en"><term>Friedreich Ataxia</term><term>Spinocerebellar Ataxias</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>Brain</term><term>Cerebellar Cortex</term><term>Cerebral Cortex</term><term>Friedreich Ataxia</term><term>Spinocerebellar Ataxias</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Brain</term><term>Cerebellar Cortex</term><term>Cerebral Cortex</term><term>Friedreich Ataxia</term><term>Spinocerebellar Ataxias</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adult</term><term>Brain Mapping</term><term>Female</term><term>Humans</term><term>Male</term><term>Reference Values</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Activité enzymatique</term><term>Ataxie spinocérébelleuse</term><term>Cortex cérébelleux</term><term>Ethanolamine kinase</term><term>Ethanolamine-phosphate cytidylytransferase</term><term>Etude comparative</term><term>Exploration</term><term>Homme</term><term>Hérédodégénérescence spinocérébelleuse Friedreich</term><term>Membrane plasmique</term><term>Métabolisme</term><term>Phospholipide</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Homme</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml: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.</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>Canada</li></country><region><li>Bavière</li><li>District de Haute-Bavière</li><li>Ontario</li></region><settlement><li>Munich</li><li>Toronto</li></settlement><orgName><li>Université Louis-et-Maximilien de Munich</li><li>Université de Toronto</li></orgName></list><tree><noCountry><name sortKey="Pandolfo, Massimo" sort="Pandolfo, Massimo" uniqKey="Pandolfo M" first="Massimo" last="Pandolfo">Massimo Pandolfo</name></noCountry><country name="Canada"><region name="Ontario"><name sortKey="Ross, Brian M" sort="Ross, Brian M" uniqKey="Ross B" first="Brian M." last="Ross">Brian M. Ross</name></region><name sortKey="Ang, Lee" sort="Ang, Lee" uniqKey="Ang L" first="Lee" last="Ang">Lee Ang</name><name sortKey="Kish, Stephen J" sort="Kish, Stephen J" uniqKey="Kish S" first="Stephen J." last="Kish">Stephen J. Kish</name><name sortKey="Kish, Stephen J" sort="Kish, Stephen J" uniqKey="Kish S" first="Stephen J." last="Kish">Stephen J. Kish</name><name sortKey="Lamarche, Jacques" sort="Lamarche, Jacques" uniqKey="Lamarche J" first="Jacques" last="Lamarche">Jacques Lamarche</name><name sortKey="Mamalias, Nikolaos" sort="Mamalias, Nikolaos" uniqKey="Mamalias N" first="Nikolaos" last="Mamalias">Nikolaos Mamalias</name><name sortKey="Moszczynska, Anna" sort="Moszczynska, Anna" uniqKey="Moszczynska A" first="Anna" last="Moszczynska">Anna Moszczynska</name><name sortKey="Ross, Brian M" sort="Ross, Brian M" uniqKey="Ross B" first="Brian M." last="Ross">Brian M. Ross</name><name sortKey="Rouleau, Guy" sort="Rouleau, Guy" uniqKey="Rouleau G" first="Guy" last="Rouleau">Guy Rouleau</name></country><country name="Allemagne"><region name="Bavière"><name sortKey="Eder, Klaus" sort="Eder, Klaus" uniqKey="Eder K" first="Klaus" last="Eder">Klaus Eder</name></region><name sortKey="Kirchgessner, Manfred" sort="Kirchgessner, Manfred" uniqKey="Kirchgessner M" first="Manfred" last="Kirchgessner">Manfred Kirchgessner</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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