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Quantitative study of mitochondrial complex I in platelets of parkinsonian patients
Author(s) -
Blandini Fabio,
Nappi Giuseppe,
Timothy Greenamyre J.
Publication year - 1998
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.870130106
Subject(s) - rotenone , platelet , parkinson's disease , substantia nigra , chemistry , levodopa , electron transport complex i , medicine , enzyme , endocrinology , biochemistry , mitochondrion , oxidoreductase , disease
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 [ 3 H]dihydrorotenone ([ 3 H]DHR), an analog of the pesticide rotenone, to complex I. We also investigated the inhibitory effect of MPP + (1‐methyl‐4‐phenyl‐pyridinium) on [ 3 H]DHR specific binding to platelet complex I. PD patients and controls showed similar levels of [ 3 H]DHR specific binding; preincubation of platelets with MPP + caused the same degree of inhibition of [ 3 H]DHR specific binding in the two groups. In PD patients, we observed a direct correlation between MPP + ‐induced inhibition of [ 3 H]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.