Dopamine, 6-hydroxydopamine, iron, and dioxygen - Their mutual interactions and possible implication in the development of Parkinson's disease

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1316

Article

Linert, W ; Herlinger, E ; Jameson, RF ; Kienzl, E ; Jellinger, K ; Youdim, MBH

关键词: Parkinson's disease;    dopamine;    6-hydroxydopamine;    iron(III);    iron(II);    manganese(II);    Fenton's reagent;    nicotine;   

DOI  :  10.1016/0925-4439(96)00020-8

来源: Elsevier

【 摘 要 】

The reactions of dopamine (1-amino-2-(3,4-dihydroxyphenyl)-ethane DA), 5-hydroxydopamine (5-OHDA), and 6-hydroxydopamine (6-OHDA), with molecular oxygen - with and without the addition of catalytic amounts of iron(III) and other metal ions - have been studied and the implication of these results with respect to the chemistry involved in the progress of Parkinson's disease is discussed, In the presence of O-2 DA reacts spontaneously without the necessity of metal-ion catalysis under the production of stoichiometric amounts of H2O2, to form initially pink dopaminochrome, which is not stable and reacts further (without the consumption of dioxygen) to form the insoluble polymeric material known as 'melanine'. DA reacts with iron(III) yielding an intermediate 1:1 complex, which decomposes releasing Fe(II) and the semiquinone, which reacts further under involvement of both Fr(III) and dioxygen. 6-OHDA reacts without showing the necessity of such an intermediate, and it is shown to be able to release iron as Fe(II) from ferritine. On the other hand, it is shown (in vitro) that Fe(II) reacts in a Fenton type reaction with DA and the present H2O2 producing 5-OHDA and especially 6-OHDA. Based on these mutual interacting reactions a mechanism for the initiation and progress of Parkinson's disease is suggested. The catalytic effects of some other transition-metal ions are presented and an explanation for the peculiarly toxic effects of manganese(II) is put forward. Finally, a possible reason for the effect that nicotine has in the mitigation of Parkinson's disease is discussed.

【 授权许可】

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