Compound 13 activates AMPK-Nrf2 signaling to protect neuronal cells from oxygen glucose deprivation-reoxygenation.
Aging (Albany NY)
; 11(24): 12032-12042, 2019 12 18.
Article
en En
| MEDLINE
| ID: mdl-31852839
ABSTRACT
Oxygen glucose deprivation-reoxygenation (OGD-R) causes the production of reactive oxygen species (ROS) and oxidative injury in neuronal cells. We tested the potential neuroprotective function of compound 13 (C13), a novel AMP-activated protein kinase (AMPK) activator, against OGD-R. We show that C13 pretreatment protected SH-SY5Y neuronal cells and primary hippocampal neurons from OGD-R. C13 activated AMPK signaling in SH-SY5Y cells and primary neurons. It significantly inhibited OGD-R-induced apoptosis activation in neuronal cells. Conversely, AMPKα1 shRNA or knockout reversed C13-mediated neuroprotection against OGD-R. C13 potently inhibited OGD-R-induced ROS production and oxidative stress in SH-SY5Y cells and primary neurons. Furthermore, C13 induced Keap1 downregulation and Nrf2 activation, causing Nrf2 stabilization, nuclear accumulation, and expression of Nrf2-dependent genes. Nrf2 silencing or knockout in SH-SY5Y cells abolished C13-mediated neuroprotection against OGD-R. In conclusion, C13 activates AMPK-Nrf2 signaling to protect neuronal cells from OGD-R.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Daño por Reperfusión
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Adenilato Quinasa
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Fármacos Neuroprotectores
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Factor 2 Relacionado con NF-E2
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Neuronas
Límite:
Animals
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Humans
Idioma:
En
Revista:
Aging (Albany NY)
Asunto de la revista:
GERIATRIA
Año:
2019
Tipo del documento:
Article
País de afiliación:
China