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Titolo:
In vivo labeling of mitochondrial complex I (NADH : ubiquinone oxidoreductase) in rat brain using [H-3]dihydrorotenone
Autore:
Talpade, DJ; Greene, JG; Higgins, DS; Greenamyre, JT;
Indirizzi:
Emory Univ, Dept Neurol, Atlanta, GA 30322 USA Emory Univ Atlanta GA USA 30322 Univ, Dept Neurol, Atlanta, GA 30322 USA Emory Univ, Dept Pharmacol, Atlanta, GA 30322 USA Emory Univ Atlanta GA USA 30322 iv, Dept Pharmacol, Atlanta, GA 30322 USA Emory Univ, Grad Program Neurosci, Atlanta, GA 30322 USA Emory Univ Atlanta GA USA 30322 d Program Neurosci, Atlanta, GA 30322 USA Ohio State Univ, Dept Neurol, Columbus, OH 43210 USA Ohio State Univ Columbus OH USA 43210 Dept Neurol, Columbus, OH 43210 USA
Titolo Testata:
JOURNAL OF NEUROCHEMISTRY
fascicolo: 6, volume: 75, anno: 2000,
pagine: 2611 - 2621
SICI:
0022-3042(200012)75:6<2611:IVLOMC>2.0.ZU;2-9
Fonte:
ISI
Lingua:
ENG
Soggetto:
ELECTRON-TRANSPORT CHAIN; CYTOCHROME-OXIDASE HISTOCHEMISTRY; HEREDITARY OPTIC NEUROPATHY; BASAL GANGLIA; SUCCINATE-DEHYDROGENASE; DIHYDROROTENONE BINDING; GLUTAMATE RECEPTORS; PARKINSONS-DISEASE; LESION; INHIBITION;
Keywords:
complex I; mitochondria; electron transport chain; [H-3]dihydrorotenone; autoradiography; in vivo; kidney; heart; liver;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
43
Recensione:
Indirizzi per estratti:
Indirizzo: Greenamyre, JT Emory Univ, Dept Neurol, 1639 Pierce Dr,WMRB 6000, Atlanta,GA 30322 USA Emory Univ 1639 Pierce Dr,WMRB 6000 Atlanta GA USA 30322 SA
Citazione:
D.J. Talpade et al., "In vivo labeling of mitochondrial complex I (NADH : ubiquinone oxidoreductase) in rat brain using [H-3]dihydrorotenone", J NEUROCHEM, 75(6), 2000, pp. 2611-2621

Abstract

Defects in mitochondrial energy metabolism have been implicated in severalneurodegenerative disorders. Defective complex I (NADH:ubiquinone oxidoreductase) activity plays a key role in Leber's hereditary optic neuropathy and, possibly, Parkinson's disease, but there is no way to assess this enzymein the living brain. We previously described an in vitro quantitative autoradiographic assay using [H-3]dihydrorotenone ([H-3]DHR) binding to complexI. We have now developed an in vivo autoradiographic assay for complex I using [H-3]DHR binding after intravenous administration. In vivo [H-3]DHR binding was regionally heterogeneous, and brain uptake was rapid. Binding wasenriched in neurons compared with glia, and white matter had the lowest levels of binding. In vivo [H-3]DHR binding was markedly reduced by local andsystemic infusion of rotenone and was enhanced by local NADH administration. There was an excellent correlation between regional levels of in vivo [H-3]DHR binding and the in vitro activities of complex II (succinate dehydrogenase) and complex IV (cytochrome oxidase), suggesting that the stoichiometry of these components of the electron transport chain is relatively constant across brain regions. The ability to assay complex I in vivo should provide a valuable tool to investigate the status of this mitochondrial enzymein the living brain and suggests potential imaging techniques for complex I in humans.

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Documento generato il 24/01/20 alle ore 12:30:08