MiR-212 Attenuates MPPâº-Induced Neuronal Damage by Targeting KLF4 in SH-SY5Y Cells.
Yonsei Med J
; 59(3): 416-424, 2018 May.
Article
em En
| MEDLINE
| ID: mdl-29611404
ABSTRACT
PURPOSE:
Parkinson's disease (PD) is a common age-dependent neurodegenerative disease. MiR-212 has been demonstrated to exert protective effects in several neurological disorders. The present study aimed to investigate the role and underlying molecular mechanism of miR-212 in PD. MATERIALS ANDMETHODS:
1-methyl-4-phenylpyridinium (MPP+)-induced SH-SY5Y cells were applied as a PD model in vitro. RT-qPCR was used to measure the expression of miR-212 and Kruppel-like factor 4 (KLF4) mRNA. Western blot analysis was performed to detect the protein levels of KLF4, Notch1 and Jagged1. Cell viability and apoptosis were determined by the Cell Counting Kit-8 and flow cytometry, respectively. Quantitative analysis of caspase-3 activity, lactate dehydrogenase (LDH), reactive oxygen species (ROS), superoxide dismutase (SOD), tumor necrosis factor-α (TNF-α), and interleukin-1 beta (IL-1ß) was conducted with corresponding ELISA kits. Dual-luciferase reporter assay was employed to evaluate the relationship between miR-212 and KLF4.RESULTS:
MiR-212 was downregulated in MPPâº-induced SH-SY5Y cells. Also, miR-212 alleviated MPPâº-induced SH-SY5Y cell damage, embodied by increased cell viability, decreased caspase-3 activity, LDH release, ROS production, TNF-α, and IL-1ß expression, as well as elevated SOD levels. KLF4 was a direct target of miR-212, and miR-212 repressed KLF4 expression in a post-transcriptional manner. Moreover, miR-212-mediated protection effects were abated following KLF4 expression restoration in MPPâº-induced SH-SY5Y cells, represented as lowered cell viability and enhanced apoptotic rate. Furthermore, Notch signaling was involved in the regulation of miR-212/KLF4 axis in MPPâº-induced SH-SY5Y cells.CONCLUSION:
miR-212 might attenuate MPPâº-induced neuronal damage by regulating KLF4/Notch signaling pathway in SH-SY5Y cells, a promising target for PD therapy.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença de Parkinson
/
Transdução de Sinais
/
1-Metil-4-fenilpiridínio
/
Substâncias Protetoras
/
MicroRNAs
/
Fatores de Transcrição Kruppel-Like
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Yonsei Med J
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
China