Mortalin inhibition in experimental Parkinson's disease
Identifieur interne : 001543 ( Main/Exploration ); précédent : 001542; suivant : 001544Mortalin inhibition in experimental Parkinson's disease
Auteurs : Davide Chiasserini [Italie] ; Alessandro Tozzi [Italie] ; Antonio De Iure [Italie] ; Michela Tantucci [Italie] ; Federica Susta [Italie] ; Pier Luigi Orvietani [Italie] ; Keizo Koya [États-Unis] ; Luciano Binaglia [Italie] ; Paolo Calabresi [Italie]Source :
- Movement Disorders [ 0885-3185 ] ; 2011-08-01.
Descripteurs français
- Pascal (Inist)
English descriptors
- KwdEn :
- 6‐hydroxydopamine, Action Potentials (drug effects), Animals, Antiparasitic Agents (therapeutic use), Cerebral Cortex (pathology), Corpus Striatum (pathology), Disease Models, Animal, Dopamine, Dose-Response Relationship, Drug, Drug Interactions, Electron Transport Complex I (metabolism), Experimental disease, Gene Expression Regulation (drug effects), HSP70 Heat-Shock Proteins (antagonists & inhibitors), HSP70 Heat-Shock Proteins (therapeutic use), Heat shock protein, In Vitro Techniques, Male, Mitochondria, Nervous system diseases, Neurons (drug effects), Oxidopamine (toxicity), Parkinson Disease (drug therapy), Parkinson Disease (etiology), Parkinson Disease (pathology), Parkinson disease, Parkinson's disease, Proteomics (methods), Pyridines (pharmacology), Rats, Rats, Wistar, Thiazoles (pharmacology), heat shock protein, mitochondria, mortalin, rotenone.
- MESH :
- chemical , antagonists & inhibitors : HSP70 Heat-Shock Proteins.
- chemical , metabolism : Electron Transport Complex I.
- chemical , pharmacology : Pyridines, Thiazoles.
- chemical , therapeutic use : Antiparasitic Agents, HSP70 Heat-Shock Proteins.
- drug effects : Action Potentials, Gene Expression Regulation, Neurons.
- drug therapy : Parkinson Disease.
- etiology : Parkinson Disease.
- methods : Proteomics.
- pathology : Cerebral Cortex, Corpus Striatum, Parkinson Disease.
- chemical , toxicity : Oxidopamine.
- Animals, Disease Models, Animal, Dose-Response Relationship, Drug, Drug Interactions, In Vitro Techniques, Male, Rats, Rats, Wistar.
Abstract
Among heat shock proteins, mortalin has been linked to the pathogenesis of Parkinson's disease. In the present work a rat model of Parkinson's disease was used to analyze the expression of striatal proteins and, more specifically, mortalin expression. The possible involvement of mortalin in Parkinson's disease pathogenesis was further investigated by utilizing an electrophysiological approach and pharmacological inhibition of mortalin in both the physiological and the parkinsonian states. Proteomic analysis was used to investigate changes in striatal protein expression in the 6‐hydroxydopamine rat model of Parkinson's disease. The electrophysiological effects of MKT‐077, a rhodamine‐123 analogue acting as an inhibitor of mortalin, were measured by field potential recordings from corticostriatal brain slices obtained from control, sham‐operated, and 6‐hydroxydopamine–denervated animals. Slices in the presence of rotenone, an inhibitor of mitochondrial complex I, were also analyzed. Proteomic analysis revealed downregulation of mortalin in the striata of 6‐hydroxydopamine–treated rats in comparison with sham‐operated animals. MKT‐077 reduced corticostriatal field potential amplitude in physiological conditions, inducing membrane depolarization and inward current in striatal medium spiny neurons. In addition, we observed that concentrations of MKT‐077 not inducing any electrophysiological effect in physiological conditions caused significant changes in striatal slices from parkinsonian animals as well as in slices treated with a submaximal concentration of rotenone. These findings suggest a critical link between mortalin function and mitochondrial activity in both physiological and pathological conditions mimicking Parkinson's disease. © 2011 Movement Disorder Society
Url:
DOI: 10.1002/mds.23647
Affiliations:
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Le document en format XML
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Maria della Misericordia, Perugia</wicri:regionArea><wicri:noRegion>Perugia</wicri:noRegion></affiliation></author><author><name sortKey="Susta, Federica" sort="Susta, Federica" uniqKey="Susta F" first="Federica" last="Susta">Federica Susta</name><affiliation wicri:level="1"><country xml:lang="fr">Italie</country><wicri:regionArea>Dipartimento di Medicina Interna, Sezione di Biochimica, Università di Perugia, Perugia</wicri:regionArea><wicri:noRegion>Perugia</wicri:noRegion></affiliation></author><author><name sortKey="Orvietani, Pier Luigi" sort="Orvietani, Pier Luigi" uniqKey="Orvietani P" first="Pier Luigi" last="Orvietani">Pier Luigi Orvietani</name><affiliation wicri:level="1"><country xml:lang="fr">Italie</country><wicri:regionArea>Dipartimento di Medicina Interna, Sezione di Biochimica, Università di Perugia, Perugia</wicri:regionArea><wicri:noRegion>Perugia</wicri:noRegion></affiliation></author><author><name sortKey="Koya, Keizo" sort="Koya, Keizo" uniqKey="Koya K" first="Keizo" last="Koya">Keizo Koya</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Synta Pharmaceuticals Corp., Lexington, Massachusetts</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Binaglia, Luciano" sort="Binaglia, Luciano" uniqKey="Binaglia L" first="Luciano" last="Binaglia">Luciano Binaglia</name><affiliation wicri:level="1"><country xml:lang="fr">Italie</country><wicri:regionArea>Dipartimento di Medicina Interna, Sezione di Biochimica, Università di Perugia, Perugia</wicri:regionArea><wicri:noRegion>Perugia</wicri:noRegion></affiliation></author><author><name sortKey="Calabresi, Paolo" sort="Calabresi, Paolo" uniqKey="Calabresi P" first="Paolo" last="Calabresi">Paolo Calabresi</name><affiliation wicri:level="1"><country xml:lang="fr">Italie</country><wicri:regionArea>Clinica Neurologica, Università degli studi di Perugia, Ospedale S. Maria della Misericordia, Perugia</wicri:regionArea><wicri:noRegion>Perugia</wicri:noRegion></affiliation><affiliation wicri:level="3"><country xml:lang="fr">Italie</country><wicri:regionArea>Fondazione S. Lucia—I.R.C.C.S., Rome</wicri:regionArea><placeName><settlement type="city">Rome</settlement><region nuts="2">Latium</region></placeName></affiliation></author></analytic><monogr></monogr><series><title level="j">Movement Disorders</title><title level="j" type="abbrev">Mov. Disord.</title><idno type="ISSN">0885-3185</idno><idno type="eISSN">1531-8257</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2011-08-01">2011-08-01</date><biblScope unit="vol">26</biblScope><biblScope unit="issue">9</biblScope><biblScope unit="page" from="1639">1639</biblScope><biblScope unit="page" to="1647">1647</biblScope></imprint><idno type="ISSN">0885-3185</idno></series><idno type="istex">50D32C6A650908F0A66D37519E1B249E0D005A43</idno><idno type="DOI">10.1002/mds.23647</idno><idno type="ArticleID">MDS23647</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>6‐hydroxydopamine</term><term>Action Potentials (drug effects)</term><term>Animals</term><term>Antiparasitic Agents (therapeutic use)</term><term>Cerebral Cortex (pathology)</term><term>Corpus Striatum (pathology)</term><term>Disease Models, Animal</term><term>Dopamine</term><term>Dose-Response Relationship, Drug</term><term>Drug Interactions</term><term>Electron Transport Complex I (metabolism)</term><term>Experimental disease</term><term>Gene Expression Regulation (drug effects)</term><term>HSP70 Heat-Shock Proteins (antagonists & inhibitors)</term><term>HSP70 Heat-Shock Proteins (therapeutic use)</term><term>Heat shock protein</term><term>In Vitro Techniques</term><term>Male</term><term>Mitochondria</term><term>Nervous system diseases</term><term>Neurons (drug effects)</term><term>Oxidopamine (toxicity)</term><term>Parkinson Disease (drug therapy)</term><term>Parkinson Disease (etiology)</term><term>Parkinson Disease (pathology)</term><term>Parkinson disease</term><term>Parkinson's disease</term><term>Proteomics (methods)</term><term>Pyridines (pharmacology)</term><term>Rats</term><term>Rats, Wistar</term><term>Thiazoles (pharmacology)</term><term>heat shock protein</term><term>mitochondria</term><term>mortalin</term><term>rotenone</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>HSP70 Heat-Shock Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Electron Transport Complex I</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Pyridines</term><term>Thiazoles</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antiparasitic Agents</term><term>HSP70 Heat-Shock Proteins</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Action Potentials</term><term>Gene Expression Regulation</term><term>Neurons</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="etiology" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Proteomics</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Cerebral Cortex</term><term>Corpus Striatum</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" type="chemical" qualifier="toxicity" xml:lang="en"><term>Oxidopamine</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Disease Models, Animal</term><term>Dose-Response Relationship, Drug</term><term>Drug Interactions</term><term>In Vitro Techniques</term><term>Male</term><term>Rats</term><term>Rats, Wistar</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Dopamine</term><term>Maladie de Parkinson</term><term>Mitochondrie</term><term>Pathologie du système nerveux</term><term>Pathologie expérimentale</term><term>Protéine choc thermique</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Among heat shock proteins, mortalin has been linked to the pathogenesis of Parkinson's disease. In the present work a rat model of Parkinson's disease was used to analyze the expression of striatal proteins and, more specifically, mortalin expression. The possible involvement of mortalin in Parkinson's disease pathogenesis was further investigated by utilizing an electrophysiological approach and pharmacological inhibition of mortalin in both the physiological and the parkinsonian states. Proteomic analysis was used to investigate changes in striatal protein expression in the 6‐hydroxydopamine rat model of Parkinson's disease. The electrophysiological effects of MKT‐077, a rhodamine‐123 analogue acting as an inhibitor of mortalin, were measured by field potential recordings from corticostriatal brain slices obtained from control, sham‐operated, and 6‐hydroxydopamine–denervated animals. Slices in the presence of rotenone, an inhibitor of mitochondrial complex I, were also analyzed. Proteomic analysis revealed downregulation of mortalin in the striata of 6‐hydroxydopamine–treated rats in comparison with sham‐operated animals. MKT‐077 reduced corticostriatal field potential amplitude in physiological conditions, inducing membrane depolarization and inward current in striatal medium spiny neurons. In addition, we observed that concentrations of MKT‐077 not inducing any electrophysiological effect in physiological conditions caused significant changes in striatal slices from parkinsonian animals as well as in slices treated with a submaximal concentration of rotenone. These findings suggest a critical link between mortalin function and mitochondrial activity in both physiological and pathological conditions mimicking Parkinson's disease. © 2011 Movement Disorder Society</div></front></TEI><affiliations><list><country><li>Italie</li><li>États-Unis</li></country><region><li>Latium</li><li>Massachusetts</li></region><settlement><li>Rome</li></settlement></list><tree><country name="Italie"><noRegion><name sortKey="Chiasserini, Davide" sort="Chiasserini, Davide" uniqKey="Chiasserini D" first="Davide" last="Chiasserini">Davide Chiasserini</name></noRegion><name sortKey="Binaglia, Luciano" sort="Binaglia, Luciano" uniqKey="Binaglia L" first="Luciano" last="Binaglia">Luciano Binaglia</name><name sortKey="Calabresi, Paolo" sort="Calabresi, Paolo" uniqKey="Calabresi P" first="Paolo" last="Calabresi">Paolo Calabresi</name><name sortKey="Calabresi, Paolo" sort="Calabresi, Paolo" uniqKey="Calabresi P" first="Paolo" last="Calabresi">Paolo Calabresi</name><name sortKey="Chiasserini, Davide" sort="Chiasserini, Davide" uniqKey="Chiasserini D" first="Davide" last="Chiasserini">Davide Chiasserini</name><name sortKey="De Iure, Antonio" sort="De Iure, Antonio" uniqKey="De Iure A" first="Antonio" last="De Iure">Antonio De Iure</name><name sortKey="De Iure, Antonio" sort="De Iure, Antonio" uniqKey="De Iure A" first="Antonio" last="De Iure">Antonio De Iure</name><name sortKey="Orvietani, Pier Luigi" sort="Orvietani, Pier Luigi" uniqKey="Orvietani P" first="Pier Luigi" last="Orvietani">Pier Luigi Orvietani</name><name sortKey="Susta, Federica" sort="Susta, Federica" uniqKey="Susta F" first="Federica" last="Susta">Federica Susta</name><name sortKey="Tantucci, Michela" sort="Tantucci, Michela" uniqKey="Tantucci M" first="Michela" last="Tantucci">Michela Tantucci</name><name sortKey="Tozzi, Alessandro" sort="Tozzi, Alessandro" uniqKey="Tozzi A" first="Alessandro" last="Tozzi">Alessandro Tozzi</name><name sortKey="Tozzi, Alessandro" sort="Tozzi, Alessandro" uniqKey="Tozzi A" first="Alessandro" last="Tozzi">Alessandro Tozzi</name></country><country name="États-Unis"><region name="Massachusetts"><name sortKey="Koya, Keizo" sort="Koya, Keizo" uniqKey="Koya K" first="Keizo" last="Koya">Keizo Koya</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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