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

Abstract

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 O2 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 Fe(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.

Neutrophil Gelatinase-Associated Lipocalin Expresses Antimicrobial Activity by Interfering withl-Norepinephrine-Mediated Bacterial Iron Acquisition

“…3C, D), and the resulting K D values of 0.40 Ϯ 0.15 and 0.52 Ϯ 0.16 nM, respectively, are in agreement with previous reports (3,25). Titration with dopamine was not possible, since its complexation with Fe 3ϩ led to a precipitate, possibly due to metal-catalyzed melanine formation (34 (Fig. 3F), which is in agreement with earlier measurements (39).…”

Inhibition of 6-hydroxydopamine-induced endoplasmic reticulum stress by sulforaphane through the activation of Nrf2 nuclear translocation

“…The generation of reactive oxygen species (ROS) is an important mediator for 6-OHDA-induced neuronal death (33,34). The production of ROS inevitably triggers stress-activated signaling pathways, including ER stress responses (35).…”

Neurodegeneration in an animal model of Parkinson's disease is exacerbated by a high-fat diet

“…7). Iron is abundant in the SN and can react in a Fenton-type reaction with DA and hydrogen peroxide (produced extensively by monoamine oxidase during DA turnover) to produce 6-OHDA (43), which, in turn, can increase iron release from ferritin (35). This suggests that 6-OHDA may play an important role in perpetuating this damaging endogenous cycle.…”