Indirubin-3-Oxime Prevents H2O2-Induced Neuronal Apoptosis via Concurrently Inhibiting GSK3ß and the ERK Pathway.
Cell Mol Neurobiol
; 37(4): 655-664, 2017 May.
Article
em En
| MEDLINE
| ID: mdl-27412761
ABSTRACT
Oxidative stress-induced neuronal apoptosis plays an important role in many neurodegenerative disorders. In this study, we have shown that indirubin-3-oxime, a derivative of indirubin originally designed for leukemia therapy, could prevent hydrogen peroxide (H2O2)-induced apoptosis in both SH-SY5Y cells and primary cerebellar granule neurons. H2O2 exposure led to the increased activities of glycogen synthase kinase 3ß (GSK3ß) and extracellular signal-regulated kinase (ERK) in SH-SY5Y cells. Indirubin-3-oxime treatment significantly reversed the altered activity of both the PI3-K/Akt/GSK3ß cascade and the ERK pathway induced by H2O2. In addition, both GSK3ß and mitogen-activated protein kinase inhibitors significantly prevented H2O2-induced neuronal apoptosis. Moreover, specific inhibitors of the phosphoinositide 3-kinase (PI3-K) abolished the neuroprotective effects of indirubin-3-oxime against H2O2-induced neuronal apoptosis. These results strongly suggest that indirubin-3-oxime prevents H2O2-induced apoptosis via concurrent inhibiting GSK3ß and the ERK pathway in SH-SY5Y cells, providing support for the use of indirubin-3-oxime to treat neurodegenerative disorders caused or exacerbated by oxidative stress.
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Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Apoptose
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Peróxido de Hidrogênio
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
China