Lack of neuroprotective effect of celastrol under conditions of proteasome inhibition by lactacystin in in vitro and in vivo studies: implications for Parkinson's disease.
Neurotox Res
; 26(3): 255-73, 2014 Oct.
Article
en En
| MEDLINE
| ID: mdl-24842651
ABSTRACT
A number of studies suggest that the ubiquitin-proteasome system (UPS) impairment may underlie neuronal death in Parkinson's disease. Celastrol is a neuroprotective agent with anti-inflammatory and antioxidant properties. The aim of this study was to determine whether celastrol may exert neuroprotective effects both in vitro and in vivo under conditions of the lactacystin-induced UPS inhibition. In the in vitro study, mouse primary cortical neurons and neuroblastoma SH-SY5Y cells were incubated with lactacystin for 48 h (2.5 and 10 µg/ml, respectively). The animal study was performed on male Wistar rats injected unilaterally with lactacystin (5 µg/2 µl) into the substantia nigra (SN) pars compacta. In the in vitro study, we did not found any protective effects of celastrol, given either in the pre- or co-treatment mode. Moreover, in the higher concentrations, celastrol itself reduced cell viability, and enhanced the lactacystin-induced cell death in both types of cells. In the in vivo study, none of the celastrol doses (0.3-3 mg/kg) attenuated the lactacystin-induced decrease in the level of dopamine (DA) and its metabolites or protected nigral dopaminergic neurons against the lactacystin-induced degeneration. The highest celastrol dose potentiated the lactacystin-induced decrease in the level of DA and its metabolites in the lesioned striatum, and accelerated the lactacystin-induced increase in the oxidative and total metabolism of DA. Moreover, when given alone, this dose of celastrol bilaterally decreased the number and/or density of dopaminergic neurons in the SN. Our results demonstrate that celastrol does not induce neuroprotective effects under conditions of UPS inhibition.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
6_ODS3_enfermedades_notrasmisibles
Problema de salud:
6_parkinson_disease
Asunto principal:
Enfermedad de Parkinson
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Acetilcisteína
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Triterpenos
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Fármacos Neuroprotectores
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Inhibidores de Proteasoma
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Neurotox Res
Asunto de la revista:
NEUROLOGIA
Año:
2014
Tipo del documento:
Article