Possible Role of Salsolinol Quinone Methide in the Decrease of RCSN-3 Cell Survival

Martinez-Alvarado, Pedro; Dagnino‐Subiabre, Alexies; Paris, Irmgard; Metodiewa, Diana; Welch, Christopher J.; Olea‐Azar, Claudio; Caviedes, Pablo; Caviedes, Raúl; Segura‐Aguilar, Juan

doi:10.1006/bbrc.2001.4907

Cited by 28 publications

(17 citation statements)

References 25 publications

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“…Furthermore, it was reported that catecholamine oxidation occurs in the brain (10) and that the oxidation of dopamine is involved in the Parkinson's disease (11,12). The oxidative stress induced by catecholamines results from their capacity to oxidize into o-quinones, which are reactive intermediates that can undergo an irreversible 1,4-intramolecular cyclization leading to the formation of aminochromes (2,3-dihydroindole-5,6-diones) (2,13).…”

Section: Introductionmentioning

confidence: 99%

Cu²⁺-Induced Isoproterenol Oxidation into Isoprenochrome in Adult Rat Calcium-Tolerant Cardiomyocytes

Remião

Carvalho

Carmo

et al. 2002

Chem. Res. Toxicol.

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Sustained high levels of circulating catecholamines may induce cardiotoxicity. There is increasing evidence that this could result from catecholamine oxidation into aminochromes, which is catalyzed by transition metals. In fact, it has already been shown that copper-induced oxidation of the beta-agonist isoproterenol decreases the viability of isolated cardiomyocytes. Thus, the aim of this work was to contribute for the clarification of the mechanisms underlying the toxic effects of isoproterenol, Cu2+ and their concomitant effect in isolated rat cardiomyocytes. Freshly isolated calcium-tolerant cardiomyocytes from adult rat were incubated with 1 mM isoproterenol, 20 microM Cu2+ or with both during 4 h. Isoproterenol and its aminochrome (isoprenochrome), and reduced and oxidized glutathione were measured at each hour in the incubation medium and in the cells. The intracellular activities of the selenium-dependent glutathione peroxidase, glutathione reductase, and glutathione-S-transferase were determined after 4 h of incubation. Isoprenochrome was found in both cells and incubation medium in samples incubated with isoproterenol alone. However, in the isoproterenol plus Cu2+ samples, a greater depletion of isoproterenol accompanied by a proportional increase of isoprenochrome was observed. This higher ISO oxidation resulted in the depletion of intracellular glutathione and in the release of oxidized glutathione to the incubation medium. The content of total glutathione (intra- and extracellular) and the intracellular activity of the selenium-dependent glutathione peroxidase, glutathione reductase, and glutathione-S-transferase were also decreased in the isoproterenol plus Cu2+ samples. These results seem to indicate that the oxidative stress resulting from catecholamine/transition metal association may contribute to catecholamine cardiotoxicity.

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Section: Introductionmentioning

confidence: 99%

Cu²⁺-Induced Isoproterenol Oxidation into Isoprenochrome in Adult Rat Calcium-Tolerant Cardiomyocytes

Remião

Carvalho

Carmo

et al. 2002

Chem. Res. Toxicol.

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“…RCSN-3 cells present immunopositive staining against dopamine, norepinephrine and serotonin transporter (FIG. Nomifensine was found to also inhibit dopamine uptake (Martinez-Alvarado et al, 2001) and dopamine-Cu complex . Nomifensine was found to also inhibit dopamine uptake (Martinez-Alvarado et al, 2001) and dopamine-Cu complex .…”

Section: Resultsmentioning

confidence: 96%

The catecholaminergic RCSN-3 cell line: A model to study dopamine metabolism

Paris¹,

Lozano²,

Cárdenas³

et al. 2008

neurotox res

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RCSN-3 cells are a cloned cell line derived from the substantia nigra of an adult rat. The cell line grows in monolayer and does not require differentiation to express catecholaminergic traits, such as (i) tyrosine hydroxylase; (ii) dopamine release; (iii) dopamine transport; (iv) norepinephrine transport; (v) monoamine oxidase (MAO)-A expression, but not MAO-B; (vi) formation of neuromelanin; (vii) VMAT-2 expression. In addition, this cell line expresses serotonin transporters, divalent metal transporter, DMT1, dopamine receptor 1 mRNA under proliferating conditions, and dopamine receptor 5 mRNA after incubation with dopamine or dicoumarol. Expression of dopamine receptors D(2), D(3) and D(4) mRNA were not detected in proliferating cells or when the cells were treated with dopamine, CuSO(4), dicoumarol or dopamine-copper complex. Angiotensin II receptor mRNA was also found to be expressed, but it underwent down regulation in the presence of aminochrome. Total quinone reductase activity corresponded 94% to DT-diaphorase. The cells also express antioxidant enzymes such as superoxide dismutase, catalase and glutathione peroxidase. This cell line is a suitable in vitro model for studies of dopamine metabolism, since under proliferating conditions the cells express all the pertinent markers.

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“…Recently, salsolinol was found to decrease survival in a concentration-dependent manner in the dopaminergic neuronal cell line RCSN-3 derived from adult rat substantia nigra. Incubation of RCSN-3 cells with salsolinol plus dicoumarol significantly decreased cell survival by 2.5-fold (Martinez-Alvarado et al, 2001). This strong effect of dicoumarol on the survival of RCSN-3 cells incubated with salsolinol supports the idea that the oxidative metabolism of salsolinol may be involved in its neurotoxic effects, since dicoumarol is a specific inhibitor of DT-diaphorase (Ernster, 1987 Research, 2004, VOL.…”

mentioning

confidence: 81%

“…Evidence of the formation of salsolinol o-semiquinone radical has been provided by ESR studies during one-electron oxidation of salsolinol catalyzed by lactoperoxidase (Martinez-Alvarado et al, 2001). DT-diaphorase is a flavoenzyme that reduces quinones to hydroquinones by transferring two electrons, preventing the formation of semiquinone radicals catalyzed by one-electron reduction of quinones (Ernster, 1987).…”

Section: Rapid Communicationmentioning

confidence: 99%

Inhibition of DT-Diaphorase potentiates thein vivo neurotoxic effect of intranigral injection of salsolinol in rats

et al. 2003

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The present study shows that intranigral injection of dicoumarol, a DT-diaphorase inhibitor, potentiates the neurotoxic effect of salsolinol (salsolinol 1.25 nmoles plus dicoumarol 2 nmoles; in 2 µl). Rats treated with dicoumarol plus salsolinol presented a characteristic contralateral rotational behaviour when they were stimulated with apomorphine (0.5 mg/kg, sc), similar to rats injected unilaterally with 6-hydroxydopamine (6-OHDA). These rats also exhibited impairment of motor and cognitive behaviours. The results support the hypothesis that DT-diaphorase plays a protective role in the nigrostriatal dopaminergic systems.

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Possible Role of Salsolinol Quinone Methide in the Decrease of RCSN-3 Cell Survival

Cited by 28 publications

References 25 publications

Cu²⁺-Induced Isoproterenol Oxidation into Isoprenochrome in Adult Rat Calcium-Tolerant Cardiomyocytes

Cu²⁺-Induced Isoproterenol Oxidation into Isoprenochrome in Adult Rat Calcium-Tolerant Cardiomyocytes

The catecholaminergic RCSN-3 cell line: A model to study dopamine metabolism

Inhibition of DT-Diaphorase potentiates thein vivo neurotoxic effect of intranigral injection of salsolinol in rats

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Possible Role of Salsolinol Quinone Methide in the Decrease of RCSN-3 Cell Survival

Cited by 28 publications

References 25 publications

Cu2+-Induced Isoproterenol Oxidation into Isoprenochrome in Adult Rat Calcium-Tolerant Cardiomyocytes

Cu2+-Induced Isoproterenol Oxidation into Isoprenochrome in Adult Rat Calcium-Tolerant Cardiomyocytes

The catecholaminergic RCSN-3 cell line: A model to study dopamine metabolism

Inhibition of DT-Diaphorase potentiates thein vivo neurotoxic effect of intranigral injection of salsolinol in rats

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Cu²⁺-Induced Isoproterenol Oxidation into Isoprenochrome in Adult Rat Calcium-Tolerant Cardiomyocytes

Cu²⁺-Induced Isoproterenol Oxidation into Isoprenochrome in Adult Rat Calcium-Tolerant Cardiomyocytes