Quantitative study of mitochondrial complex I in platelets of parkinsonian patients
Identifieur interne : 004F12 ( Main/Exploration ); précédent : 004F11; suivant : 004F13Quantitative study of mitochondrial complex I in platelets of parkinsonian patients
Auteurs : Blandini [Italie] ; Giuseppe Nappi [Italie] ; J. Timothy Greenamyre [États-Unis]Source :
- Movement Disorders [ 0885-3185 ] ; 1998-01.
English descriptors
- KwdEn :
- 1-Methyl-4-phenylpyridinium (pharmacology), 1‐Methyl‐4‐phenyl‐pyridinium (MPP+), Aged, Aged, 80 and over, Blood Platelets (drug effects), Blood Platelets (enzymology), Case-Control Studies, Complex I, Dopamine Agents (pharmacology), Dose-Response Relationship, Drug, Electron Transport Complex I, Energy metabolism, Female, Humans, Insecticides (metabolism), Male, Middle Aged, Mitochondria, Mitochondria (drug effects), Mitochondria (enzymology), NADH, NADPH Oxidoreductases (blood), NADH, NADPH Oxidoreductases (metabolism), Neurotoxins (pharmacology), Parkinson Disease (blood), Parkinson Disease (enzymology), Parkinson's disease, Platelet, Radioligand Assay, Rotenone (analogs & derivatives), Rotenone (metabolism), [3H]Dihydrorotenone.
- 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.
Url:
DOI: 10.1002/mds.870130106
Affiliations:
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Mondino Neurological Institute, University of Pavia, Pavia</wicri:regionArea><wicri:noRegion>Pavia</wicri:noRegion></affiliation></author><author><name sortKey="Nappi, Giuseppe" sort="Nappi, Giuseppe" uniqKey="Nappi G" first="Giuseppe" last="Nappi">Giuseppe Nappi</name><affiliation wicri:level="1"><country xml:lang="fr">Italie</country><wicri:regionArea>C. Mondino Neurological Institute, University of Pavia, Pavia</wicri:regionArea><wicri:noRegion>Pavia</wicri:noRegion></affiliation></author><author><name sortKey="Timothy Greenamyre, J" sort="Timothy Greenamyre, J" uniqKey="Timothy Greenamyre J" first="J." last="Timothy Greenamyre">J. 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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></TEI><affiliations><list><country><li>Italie</li><li>États-Unis</li></country><region><li>Géorgie (États-Unis)</li></region></list><tree><country name="Italie"><noRegion><name sortKey="Blandini" sort="Blandini" uniqKey="Blandini" last="Blandini">Blandini</name></noRegion><name sortKey="Nappi, Giuseppe" sort="Nappi, Giuseppe" uniqKey="Nappi G" first="Giuseppe" last="Nappi">Giuseppe Nappi</name></country><country name="États-Unis"><region name="Géorgie (États-Unis)"><name sortKey="Timothy Greenamyre, J" sort="Timothy Greenamyre, J" uniqKey="Timothy Greenamyre J" first="J." last="Timothy Greenamyre">J. Timothy Greenamyre</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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