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Tytuł oryginału:
Oxidation of dopamine to aminochrome as a mechanism for neurodegeneration of dopaminergic systems in Parkinson's disease. Possible neuroprotective role of DT-diaphorase.
Autorzy:
Graumann
Rebecca,
Paris
Irmgard,
Martinez-Alvorado
Pedro,
Rumanwue
Pamela,
Perez-Pastene
Carolina,
Cardenas
Sergio P.,
Marin
Pablo,
Diaz-Grez
Fernando,
Caviedes
Raul,
Caviedes
Pablo,
Segura-Aguilar
Juan
Źródło:
Pol. J. Pharmacol. 2002: 54 (6) s.573-579, il., bibliogr. 32 poz.
Sygnatura GBL:
313,156
Hasła klasyfikacyjne GBL:
neurologia
Typ dokumentu:
tytuł obcojęzyczny
Wskaźnik treści:
ludzie
zwierzęta
szczury
Streszczenie angielskie:
Although it is generally accepted that free radicals are involved in the neurodegenerative process occurring in the dopaminergic neurons of the nigro-striatal system in Parkinson's disease, the exact mechanims of neurodegeneration in vivo is still unknown. We propose that the degeneration of dopaminergic nigrostriatal system in this condition may depend on: (a) existence of free dopamine which oxidizes to aminochrome as a consequence of: (i) overproduction of dopamine, (ii) inhibition and/or low expression of synaptic vesicle catecholamine transporter, (iii) inhibition or low expression of monoamine oxidases; (b) one-electron reduction of aminochrome to leukoaminochrome o-semiquinone radical, which induces neurotoxicity, due to inhibition of DT-diaphorase or the existence of a polymorphism wiht a point mutation (C- T) in the cDNA 609 expressing an inactive DT-diaphorase. We suggest that DT-diaphorase plays an neuroprotective role in dopaminergic neurons, which is supported by the following observations: (i) Cu-toxicity is dependent on DT-diaphorase inhibition with diocoumarol in RCSN-3 cells derived from the substantia nigra, (ii) the cytotoxic effect of monoamine oxidase-A inhbitor amiflamine in RCSN-3 cells is increased by 2.4-fold (p 0.001) in the presence of the inhibitor of DT-diaphorase, dicoumarol, (iii) concomitant intracerebral administration of manganese (Mn3+) together with the DT-diaphorase inhibitor dicoumarol into the left medial forebrain bundle produced a behavioral pattern characterized by contralateral rotational behavior when the rats were stimulated...
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