| Autor: |
Christian Arriagada, Irmgard Paris, Maria Jose Sanchez de las Matas, Pedro Martinez-Alvarado, Sergio Cardenas, Patricia Castañeda, Rebecca Graumann, Carolina Perez-Pastene, Claudio Olea-Azar, Eduardo Couve, Maria T Herrero, Pablo Caviedes, Juan Segura-Aguilar |
| Jazyk: |
angličtina |
| Rok vydání: |
2004 |
| Předmět: |
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| Zdroj: |
Neurobiology of Disease, Vol 16, Iss 2, Pp 468-477 (2004) |
| Druh dokumentu: |
article |
| ISSN: |
1095-953X |
| DOI: |
10.1016/j.nbd.2004.03.014 |
| Popis: |
Leukoaminochrome o-semiquinone radical is generated during one-electron reduction of dopamine oxidation product aminochrome when DT-diaphorase is inhibited. Incubation of 100 μM aminochrome with 100 μM 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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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Full Text from ScienceDirect