Quantitative study of mitochondrial complex I in platelets of parkinsonian patients.
Identifieur interne : 004E61 ( Ncbi/Curation ); précédent : 004E60; suivant : 004E62Quantitative study of mitochondrial complex I in platelets of parkinsonian patients.
Auteurs : F. Blandini [Italie] ; G. Nappi ; J T GreenamyreSource :
- Movement disorders : official journal of the Movement Disorder Society [ 0885-3185 ] ; 1998.
English descriptors
- KwdEn :
- 1-Methyl-4-phenylpyridinium (pharmacology), Aged, Aged, 80 and over, Blood Platelets (drug effects), Blood Platelets (enzymology), Case-Control Studies, Dopamine Agents (pharmacology), Dose-Response Relationship, Drug, Electron Transport Complex I, Female, Humans, Insecticides (metabolism), Male, Middle Aged, Mitochondria (drug effects), Mitochondria (enzymology), NADH, NADPH Oxidoreductases (blood), NADH, NADPH Oxidoreductases (metabolism), Neurotoxins (pharmacology), Parkinson Disease (blood), Parkinson Disease (enzymology), Radioligand Assay, Rotenone (analogs & derivatives), Rotenone (metabolism).
- MESH :
- chemical , analogs & derivatives : Rotenone.
- chemical , blood : NADH, NADPH Oxidoreductases.
- chemical , metabolism : Insecticides, NADH, NADPH Oxidoreductases, Rotenone.
- chemical , pharmacology : 1-Methyl-4-phenylpyridinium, Dopamine Agents, Neurotoxins.
- blood : Parkinson Disease.
- drug effects : Blood Platelets, Mitochondria.
- enzymology : Blood Platelets, Mitochondria, Parkinson Disease.
- Aged, Aged, 80 and over, Case-Control Studies, Dose-Response Relationship, Drug, Electron Transport Complex I, Female, Humans, Male, Middle Aged, Radioligand Assay.
Abstract
Activity of mitochondrial enzyme complex I (NADH-ubiquinone oxidoreductase) is reduced in the substantia nigra of patients with Parkinson's disease (PD). A less pronounced decrease in the activity of this enzyme has also been reported in platelets of PD patients. To obtain quantitative information on platelet complex I in PD, we studied platelet complex I in 16 PD patients and 16 age-matched controls by using a newly developed technique based on the binding of [3H]dihydrorotenone ([3H]DHR), an analog of the pesticide rotenone, to complex I. We also investigated the inhibitory effect of MPP+ (1-methyl-4-phenyl-pyridinium) on [3H]DHR specific binding to platelet complex I. PD patients and controls showed similar levels of [3H]DHR specific binding; preincubation of platelets with MPP+ caused the same degree of inhibition of [3H]DHR specific binding in the two groups. In PD patients, we observed a direct correlation between MPP+-induced inhibition of [3H]DHR specific binding and the daily intake of levodopa, which may be related to drug-induced changes in the transport of MPP+ into the platelet or in its binding to complex I. These findings demonstrate that the reported reduction in complex I activity in platelets of PD patients can not be accounted for by an abnormality at the level of the rotenone binding site (putatively the ND-1 gene product), although they do not exclude differences in complex I activity between PD patients and controls.
DOI: 10.1002/mds.870130106
PubMed: 9452319
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pubmed:9452319Le document en format XML
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<wicri:noRegion>University of Pavia</wicri:noRegion>
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<author><name sortKey="Nappi, G" sort="Nappi, G" uniqKey="Nappi G" first="G" last="Nappi">G. Nappi</name>
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<author><name sortKey="Greenamyre, J T" sort="Greenamyre, J T" uniqKey="Greenamyre J" first="J T" last="Greenamyre">J T Greenamyre</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">Quantitative study of mitochondrial complex I in platelets of parkinsonian patients.</title>
<author><name sortKey="Blandini, F" sort="Blandini, F" uniqKey="Blandini F" first="F" last="Blandini">F. Blandini</name>
<affiliation wicri:level="1"><nlm:affiliation>C. Mondino Neurological Institute, University of Pavia, Italy.</nlm:affiliation>
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<author><name sortKey="Nappi, G" sort="Nappi, G" uniqKey="Nappi G" first="G" last="Nappi">G. Nappi</name>
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<author><name sortKey="Greenamyre, J T" sort="Greenamyre, J T" uniqKey="Greenamyre J" first="J T" last="Greenamyre">J T Greenamyre</name>
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<series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title>
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<imprint><date when="1998" type="published">1998</date>
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<term>Aged</term>
<term>Aged, 80 and over</term>
<term>Blood Platelets (drug effects)</term>
<term>Blood Platelets (enzymology)</term>
<term>Case-Control Studies</term>
<term>Dopamine Agents (pharmacology)</term>
<term>Dose-Response Relationship, Drug</term>
<term>Electron Transport Complex I</term>
<term>Female</term>
<term>Humans</term>
<term>Insecticides (metabolism)</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Mitochondria (drug effects)</term>
<term>Mitochondria (enzymology)</term>
<term>NADH, NADPH Oxidoreductases (blood)</term>
<term>NADH, NADPH Oxidoreductases (metabolism)</term>
<term>Neurotoxins (pharmacology)</term>
<term>Parkinson Disease (blood)</term>
<term>Parkinson Disease (enzymology)</term>
<term>Radioligand Assay</term>
<term>Rotenone (analogs & derivatives)</term>
<term>Rotenone (metabolism)</term>
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<keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en"><term>Rotenone</term>
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<term>NADH, NADPH Oxidoreductases</term>
<term>Rotenone</term>
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<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>1-Methyl-4-phenylpyridinium</term>
<term>Dopamine Agents</term>
<term>Neurotoxins</term>
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<keywords scheme="MESH" qualifier="blood" xml:lang="en"><term>Parkinson Disease</term>
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<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Blood Platelets</term>
<term>Mitochondria</term>
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<keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>Blood Platelets</term>
<term>Mitochondria</term>
<term>Parkinson Disease</term>
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<keywords scheme="MESH" xml:lang="en"><term>Aged</term>
<term>Aged, 80 and over</term>
<term>Case-Control Studies</term>
<term>Dose-Response Relationship, Drug</term>
<term>Electron Transport Complex I</term>
<term>Female</term>
<term>Humans</term>
<term>Male</term>
<term>Middle Aged</term>
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<front><div type="abstract" xml:lang="en">Activity of mitochondrial enzyme complex I (NADH-ubiquinone oxidoreductase) is reduced in the substantia nigra of patients with Parkinson's disease (PD). A less pronounced decrease in the activity of this enzyme has also been reported in platelets of PD patients. To obtain quantitative information on platelet complex I in PD, we studied platelet complex I in 16 PD patients and 16 age-matched controls by using a newly developed technique based on the binding of [3H]dihydrorotenone ([3H]DHR), an analog of the pesticide rotenone, to complex I. We also investigated the inhibitory effect of MPP+ (1-methyl-4-phenyl-pyridinium) on [3H]DHR specific binding to platelet complex I. PD patients and controls showed similar levels of [3H]DHR specific binding; preincubation of platelets with MPP+ caused the same degree of inhibition of [3H]DHR specific binding in the two groups. In PD patients, we observed a direct correlation between MPP+-induced inhibition of [3H]DHR specific binding and the daily intake of levodopa, which may be related to drug-induced changes in the transport of MPP+ into the platelet or in its binding to complex I. These findings demonstrate that the reported reduction in complex I activity in platelets of PD patients can not be accounted for by an abnormality at the level of the rotenone binding site (putatively the ND-1 gene product), although they do not exclude differences in complex I activity between PD patients and controls.</div>
</front>
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