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

Arriagada, Christian; Paris, Irmgard; Matas, M. J. Sánchez De Las; Martinez-Alvarado, Pedro; Cárdenas, Sergio; Castañeda, Patricia; Graumann, Rebecca; Perez-Pastene, Carolina; Olea‐Azar, Claudio; Couve, Eduardo; Herrero, M.T.; Caviedes, Pablo; Segura‐Aguilar, Juan

doi:10.1016/j.nbd.2004.03.014

Cited by 108 publications

(115 citation statements)

References 40 publications

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“…NQO1 is known to metabolize aminochrome and dopachrome (Segura-Aguilar and Lind, 1989;Baez et al, 1994), has been located in both rat (Schultzberg et al, 1988) and human mesencephalic tissue (van Muiswinkel et al, 2004), and has also been found to be elevated in the substantia nigra pars compacta of parkinsonian brains (van Muiswinkel et al, 2004). A neuroprotective role for NQO1 against aminochrome-dependent toxicity is supported by previous work in catecholaminergic cell lines (Paris et al, 2001(Paris et al, , 2005Arriagada et al, 2004) and in vivo in rats (Diaz-Veliz et al, 2002;Segura-Aguilar et al, 2004). There is conflicting evidence regarding the relationship of NQO1 polymorphisms to the incidence of PD (Harada et al, 2001;Shao et al, 2001), but the elevation of enzyme levels in the target cells for PD in parkinsonian brains suggested that it may play a protective role (van Muiswinkel et al, 2004).…”

Section: Discussionmentioning

confidence: 71%

A Potential Role for Cyclized Quinones Derived from Dopamine, DOPA, and 3,4-Dihydroxyphenylacetic Acid in Proteasomal Inhibition

Zafar¹,

Siegel²,

Ross³

2006

Mol Pharmacol

105

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We examined the ability of oxidation products of dopamine, DOPA, and 3,4-dihydroxyphenylacetic acid (DOPAC) to inhibit proteasomal activity. Dopamine, DOPA, and DOPAC underwent tyrosinase-catalyzed oxidation to generate aminochrome, dopachrome, and furanoquinone, respectively. In these studies, the oxidation of dopamine by tyrosinase generated product(s) that inhibited the proteasome, and proteasomal inhibition correlated with the presence of the UV-visible spectrum of aminochrome. The addition of superoxide dismutase and catalase did not prevent proteasomal inhibition. The addition of NADH and the quinone reductase NAD(P)H:quinone oxidoreductase 1 (NQO1) protected against aminochromeinduced proteasome inhibition. Although NQO1 protected against dopamine-induced proteasomal inhibition, the metabolism of aminochrome by NQO1 led to oxygen uptake because of the generation of a redox-labile cyclized hydroquinone, further demonstrating the lack of involvement of oxygen radicals in proteasomal inhibition. DOPA underwent tyrosinase-catalyzed oxidation to form dopachrome, and similar to aminochrome, proteasomal inhibition correlated with the presence of a dopachrome UV-visible spectrum. The inclusion of NQO1 did not protect against proteasomal inhibition induced by dopachrome. Oxidation of DOPAC by tyrosinase generated furanoquinone, which was a poor proteasome inhibitor. These studies demonstrate that oxidation products, including cyclized quinones derived from dopamine and related compounds, rather than oxygen radicals have the ability to inhibit the proteasome. They also suggest an important protective role for NQO1 in protecting against dopamine-induced proteasomal inhibition. The ability of endogenous intermediates formed during dopaminergic metabolism to cause proteasomal inhibition provides a potential basis for the selectivity of dopaminergic neuron damage in Parkinson's disease.Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by destruction of dopamine containing neurons in the substantia nigra pars compacta coupled with the formation of neuronal cytoplasmic inclusions known as Lewy bodies (Olanow and Tatton, 1999). Several lines of evidence have implicated failure of the ubiquitin proteasomal system (UPS) as central in the pathogenesis of PD, and a number of excellent, recent reviews have summarized the evidence linking defects in the UPS to both familial and sporadic PD

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Section: Discussionmentioning

confidence: 71%

A Potential Role for Cyclized Quinones Derived from Dopamine, DOPA, and 3,4-Dihydroxyphenylacetic Acid in Proteasomal Inhibition

Zafar¹,

Siegel²,

Ross³

2006

Mol Pharmacol

105

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“…However, dopaminochrome has also been shown to be responsible (229) for the inhibition of R-synuclein fibrillization seen for dopamine (230), suggesting that dopamine depletion in PD would enhance R-synuclein aggregation. Dopaminochrome and its one-electron-reduced semiquinone constitute an active redox cycling pair that is toxic to dopaminergic neurons in culture, resulting in hydroxyl radical production, mitochondrial damage, and necrotic cell death (231). Dopaminochrome-mediated redox cycling also plays a role in the selective catecholaminergic toxicity of copper (232) and iron (233), initiated by the uptake of the metal ion complexes of dopamine via the catecholamine transporter.…”

Section: Role Of Oxidative Stress In the Pathogenesis Of Pd And Modelmentioning

confidence: 99%

Oxidative Stress and Neurotoxicity

Sayre

Perry

Smith

2007

Chem. Res. Toxicol.

728

494

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There is increasing awareness of the ubiquitous role of oxidative stress in neurodegenerative disease states. A continuing challenge is to be able to distinguish between oxidative changes that occur early in the disease from those that are secondary manifestations of neuronal degeneration. This perspective highlights the role of oxidative stress in Alzheimer's, Parkinson's, and Huntington's diseases, amyotrophic lateral sclerosis, and multiple sclerosis, neurodegenerative and neuroinflammatory disorders where there is evidence for a primary contribution of oxidative stress in neuronal death, as opposed to other diseases where oxidative stress more likely plays a secondary or by-stander role. We begin with a brief review of the biochemistry of oxidative stress as it relates to mechanisms that lead to cell death, and why the central nervous system is particularly susceptible to such mechanisms. Following a review of oxidative stress involvement in individual disease states, some conclusions are provided as to what further research should hope to accomplish in the field.

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“…On the other hand, the formation of the intermediate product during the conversion of AC to DHI is distinguished by a ΔG value that is reduced by -13.0 kJ/mol (difference in energy between AC and IM-AC shown in Scheme 2, the free energy change is also -16.0 kJ/mol) compared to the conversion of the same intermediate product leading to the formation of DHI. This indicates that excess amount of AC may stay inside the cell which could result in the conversion of AC to other reactive species and further leading to hindrance of the synthesis of melanin and neurotoxicity as also indicated in the experimental findings [50][51][52].…”

Section: Reaction Channels 1 Andmentioning

confidence: 93%

Diversion of the melanin synthetic pathway by dopamine product scavengers: A quantum chemical modeling of the reaction mechanisms

Demissie¹,

Ashebir²

2017

Bull. Chem. Soc. Eth.

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ABSTRACT. We report the stability and reactivity of the oxidation products as well as L-cysteine and Nacetylcysteine adducts of dopamine studied using quantum chemical calculations. The overall reactions studied were subdivided into four reaction channels. The first reaction channel is the oxidation of dopamine to form dopaminoquinone. The second reaction channel leads to melanin formation through subsequent reactions. The third and fourth reaction channels are reactions leading to the formation of dopaminoquinone adducts which are aimed to divert the synthesis of melanin. The results indicate that L-cysteine and N-acetylcysteine undergo chemical reactions mainly at C5 position of dopaminoquinone. The analyses of the thermodynamic energies indicate that L-cysteine and N-acetylcysteine covalently bind to dopaminoquinone by competing with the internal cyclization reaction of dopaminoquinone which leads to the synthesis of melanin. The analysis of the results, based on the reaction free energies, is also supported by the investigation of the natural bond orbitals of the reactants and products.

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

Cited by 108 publications

References 40 publications

A Potential Role for Cyclized Quinones Derived from Dopamine, DOPA, and 3,4-Dihydroxyphenylacetic Acid in Proteasomal Inhibition

A Potential Role for Cyclized Quinones Derived from Dopamine, DOPA, and 3,4-Dihydroxyphenylacetic Acid in Proteasomal Inhibition

Oxidative Stress and Neurotoxicity

Diversion of the melanin synthetic pathway by dopamine product scavengers: A quantum chemical modeling of the reaction mechanisms

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