On the mechanism of the Mn3+-induced neurotoxicity of dopamine: Prevention of quinone-derived oxygen toxicity by DT diaphorase and superoxide dismutase

Segura‐Aguilar, Juan; Lind, Christina

doi:10.1016/0009-2797(89)90006-9

Cited by 176 publications

(115 citation statements)

References 27 publications

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“…2B). Previous work has shown that aminochrome could be reduced by NQO1 in the presence of NAD(P)H and that the resultant hydroquinone was unstable to O 2 and underwent rapid redox cycling (Segura-Aguilar and Lind, 1989). We confirmed these data using our experimental conditions and observed a substantial decrease in the absorbance of aminochrome at 475 nm upon the addition of NADH and NQO1 (data not shown).…”

Section: Proteasome Inhibition By Oxidation Products Of Dopamine Resultssupporting

confidence: 89%

“…One of the significant findings in this study was that NQO1 protected against dopamine-induced proteasomal impairment. 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).…”

Section: Discussionmentioning

confidence: 67%

“…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). However, van Muiswinkel et al (2004) pointed out that NQO1 may also contribute to dopamine-induced pathology as a result of the generation of redox unstable hydroquinones, which can redox cycle (Segura-Aguilar and Lind, 1989;Baez et al, 1994). At least with respect to proteasomal inhibition, our data suggest that NQO1 plays a protective role against dopamine-derived quinones, and this conclusion is strengthened by the recent observation that NQO1 also protects against dopamine-induced apoptosis (Inayat-Hussain et al, 2005) .…”

Section: Discussionmentioning

confidence: 99%

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

Zafar¹,

Siegel²,

Ross³

2006

Mol Pharmacol

106

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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: Proteasome Inhibition By Oxidation Products Of Dopamine Resultssupporting

confidence: 89%

Section: Discussionmentioning

confidence: 67%

Section: Discussionmentioning

confidence: 99%

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

Zafar¹,

Siegel²,

Ross³

2006

Mol Pharmacol

106

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“…oxidation of DA by Mn 21 . Indeed, in vitro studies on the mechanism of Mn 2/31 -induced oxidation of DA revealed that DA is rapidly and irreversibly oxidized by Mn 31 to its cyclized orthoquinone, resulting in decreased levels of DA, but does not generate reactive oxygen species since oxygen is neither consumed nor required in this reaction (1,51). In conclusion, a similar process seems to occur in vivo.…”

Section: Figmentioning

confidence: 75%

“…On the other hand, it has been reported that lipid peroxidation is inhibited by Mn 21 both in vitro (11,60) and in postmortem brain tissues of Mn 21 -exposed rats (16,53). In addition, in vitro studies have shown that Mn produces irreversible DA depletion by oxidation to quinones without the formation of reactive oxygen species (1,51).…”

Section: Introductionmentioning

confidence: 99%

Manganese-Induced Hydroxyl Radical Formation in Rat Striatum Is Not Attenuated by Dopamine Depletion or Iron Chelationin Vivo

Sloot

Korf²,

Koster

et al. 1996

Experimental Neurology

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The present studies were aimed at investigating the possible roles of dopamine (DA) and iron in production of hydroxyl radicals ( · OH) in rat striatum after Mn 21 intoxication. For this purpose, DA depletions were assessed concomitant with in vivo 2,3-and 2,5-dihydroxybenzoic acid (DHBA) formation from the reaction of salicylate with · OH, of which 2,3-DHBA is a nonenzymatic adduct. Following intrastriatal Mn 21 injection, marked 2,3-DHBA increases were observed in a time-and dose-dependent fashion reaching maximum levels at 6-18 h and a plateau beyond 0.4 mmol

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Pro‐ and Antioxidant Functions of Quinones and Quinone Reductases in Mammalian Cells

Cadenas¹,

Hochstein²,

Ernster³

1992

Advances in Enzymology - And Related Areas of Molecular Biology

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On the mechanism of the Mn3+-induced neurotoxicity of dopamine: Prevention of quinone-derived oxygen toxicity by DT diaphorase and superoxide dismutase

Cited by 176 publications

References 27 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

Manganese-Induced Hydroxyl Radical Formation in Rat Striatum Is Not Attenuated by Dopamine Depletion or Iron Chelationin Vivo

Pro‐ and Antioxidant Functions of Quinones and Quinone Reductases in Mammalian Cells

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