Biglycan, a Nitric Oxide-Downregulated Proteoglycan, Prevents Nitric Oxide-Induced Neuronal Cell Apoptosis via Targeting Erk1/2 and p38 Signaling Pathways.
J Mol Neurosci
; 66(1): 68-76, 2018 Sep.
Article
em En
| MEDLINE
| ID: mdl-30088173
ABSTRACT
Nitric oxide (NO), a gaseous signaling molecule, induces apoptosis and mediates neurodegenerative diseases and brain injury. Biglycan (BGN), a member of the small leucine-rich proteoglycan family, was demonstrated to exert anti-apoptosis function in various disease models. However, little is known about the effect of BGN on NO-induced neurotoxicity. Here, for the first time, we reported that BGN protects against NO-induced apoptosis in human neuroblastoma SH-EP1 cells. This is supported by the finding that sodium nitroprusside (SNP), a NO donor, triggered downregulation of BGN in SH-EP1 cells, and over-expression of BGN strikingly attenuated NO-induced nuclear fragmentation and apoptosis of neuronal cells. More importantly, BGN remarkably blocked NO-induced phosphorylation of Erk1/2 and p38 signaling, but not JNK MAPK pathway in neuronal cells. Furthermore, inhibiting Erk1/2 by U0126 or p38 by SB203580 partially protected against NO-induced cell death. Conversely, downregulation of BGN by siRNA aggravated NO-induced neuronal cell death, which was not attenuated by U0126 or SB203580. These findings indicated that BGN, downregulated by NO, prevents NO-induced neuronal cell apoptosis via targeting Erk1/2 and p38 signaling pathways. Our results strongly suggest that BGN could be explored for the prevention of NO-induced neurodegenerative disorders.
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Base de dados:
MEDLINE
Assunto principal:
Apoptose
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Sistema de Sinalização das MAP Quinases
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Biglicano
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Neurônios
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article