Overexpression of MicroRNA-133a Inhibits Apoptosis and Autophagy in a Cell Model of Parkinson's Disease by Downregulating Ras-Related C3 Botulinum Toxin Substrate 1 (RAC1).
Med Sci Monit
; 26: e922032, 2020 Jul 27.
Article
en En
| MEDLINE
| ID: mdl-32713934
ABSTRACT
BACKGROUND Parkinson's disease (PD) is a movement disorder. microRNA (miR)-133 expression is reduced in PD patients and in mice with a dopamine neuron deficiency. We aimed to identify the mechanism of miR-133a in apoptosis and autophagy in PD. MATERIAL AND METHODS The optimal concentration of MPP⺠(1-methyl-4-phenylpyridinium ion) was initially determined to construct a PD cell model. Gain-of function experiments were carried out to evaluate the role of miR-133a in PD. The levels of miR-133a, RAC1 (Ras-related C3 botulinum toxin substrate 1), apoptosis-related factors, and autophagy-related factors were detected after detection of cell proliferation, cell cycle, and apoptosis. Transmission electron microscopy was applied to observe autophagosomes, and immunofluorescence staining was performed to detect LC3 and further analyze the effect of miR-133a on autophagy in a PD cell model. RESULTS Low miR-133a expression was detected in a cell model of MPPâº-induced PD. After overexpressing miR-133a, cell proliferation increased, and apoptosis (cleaved caspase-3 and Bax levels decreased, while Bcl2 levels increased) and autophagy was inhibited (LC3II/I and Beclin-1 levels decreased, while p62 levels increased). MiR-133a targeted RAC1. RACY upregulation attenuated the inhibitory effects of miR-133a on PC12 cell apoptosis and autophagy. CONCLUSIONS Our data highlighted that miR-133a overexpression prevented apoptosis and autophagy in a cell model of MPPâº-induced PD by inhibiting RAC1 expression.
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
/
MicroARNs
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Med Sci Monit
Asunto de la revista:
MEDICINA
Año:
2020
Tipo del documento:
Article