SC79, a novel Akt activator, protects dopaminergic neuronal cells from MPP+ and rotenone.
Mol Cell Biochem
; 461(1-2): 81-89, 2019 Nov.
Article
em En
| MEDLINE
| ID: mdl-31342299
In pathogenesis of Parkinson's disease (PD), mitochondrial dysfunction causes substantial reactive oxygen species (ROS) production and oxidative stress, leading to dopaminergic (DA) neuronal cell death. Mitochondrial toxins, including MPP+ (1-methyl-4-phenylpyridinium ion) and rotenone, induce oxidative injury in cultured DA neuronal cells. The current study tested the potential effect of SC79, a first-in-class small-molecule Akt activator, against the process. In SH-SY5Y cells and primary murine DA neurons, SC79 significantly attenuated MPP+- and rotenone-induced viability reduction, cell death, and apoptosis. SC79 activated Akt signaling in DA neuronal cells. Akt inhibition (by LY294002 and MK-2206) or CRISPR-Cas9-mediated Akt1 knockout completely abolished SC79-induced DA neuroprotection against MPP+. Further studies demonstrated that SC79 attenuated MPP+- and rotenone-induced ROS production, mitochondrial depolarization, and lipid peroxidation in SH-SY5Y cells and primary DA neurons. Moreover, upregulation of Nrf2-dependent genes (HO1 and NQO1) and Nrf2 protein stabilization were detected in SC79-treated SH-SY5Y cells and primary DA neurons. Together we show that SC79 protects DA neuronal cells from mitochondrial toxins possibly via activation of Akt-Nrf2 signaling.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Rotenona
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Benzopiranos
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1-Metil-4-fenilpiridínio
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Fármacos Neuroprotetores
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Ativadores de Enzimas
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Proteínas Proto-Oncogênicas c-akt
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Neurônios Dopaminérgicos
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Acetatos
Limite:
Animals
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Humans
Idioma:
En
Revista:
Mol Cell Biochem
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
China