On the neurotoxicity mechanism of leukoaminochrome o-semiquinone radical derived from dopamine oxidation: mitochondria damage, necrosis, and hydroxyl radical formation

Arriagada C.; Paris, I; de las Matas, MJS; Martinez-Alvarado, P; Cardenas, S; Castañeda P.; Graumann R; Perez-Pastene, C; Olea Azar C.; Couve, E.; Herrero, MT; Caviedes P.; Segura-Aguilar, J

Abstract

Leukoaminochrome o-semiquinone radical is generated during one-electron reduction of dopamine oxidation product aminochrome when DT-diaphorase is inhibited. Incubation of 100 ?M aminochrome with 100 ?M dicoumarol, an inhibitor of DT-diaphorase during 2 h, induces 56% cell death (P < 0.001) with concomitant formation of (i) intracellular hydroperoxides (4.2-fold increase compared to control; P < 0.001); (ii) hydroxyl radicals, detected with ESR and spin trapping agents (2.4-fold increase when cells were incubated with aminochrome in the presence of dicoumarol compared to aminochrome alone); (iii) intracellular edema, and cell membrane deterioration determined by transmission electron microscopy; (iv) absence of apoptosis, supported by using anexin-V with flow cytometry; (v) a strong decrease of mitochondrial membrane potential determined by the fluorescent dye 5,5?,6,6?-tetrachloro-1, 1?,3,3?-tetraethylbenzimidazolylcarbocyanineiodide (P < 0.01); (vi) swelling and disruption of outer and inner mitochondrial membranes determined by transmission electron microscopy. These results support the proposed role of leukoaminochrome o-semiquinone radical as neurotoxin in Parkinson's disease neurodegeneration and DT-diaphorase as neuroprotective enzyme. © 2004 Elsevier Inc. All rights reserved.

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Título según WOS: On the neurotoxicity mechanism of leukoaminochrome o-semiquinone radical derived from dopamine oxidation: mitochondria damage, necrosis, and hydroxyl radical formation
Título según SCOPUS: On the neurotoxicity mechanism of leukoaminochrome o-semiquinone radical derived from dopamine oxidation: Mitochondria damage, necrosis, and hydroxyl radical formation
Título de la Revista: NEUROBIOLOGY OF DISEASE
Volumen: 16
Número: 2
Editorial: ACADEMIC PRESS INC ELSEVIER SCIENCE
Fecha de publicación: 2004
Página de inicio: 468
Página final: 477
Idioma: English
DOI:

10.1016/j.nbd.2004.03.014

Notas: ISI, SCOPUS