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Biochem Cell Biol ; 99(5): 527-535, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34424795

RESUMO

This study explored the molecular mechanism behind the protective effects from low-dose lipopolysaccharide (LPS) on an in-vitro model of spinal cord injury (SCI). For this, PC12 cells were treated with different concentrations of LPS and the cell counting kit-8 assay was used to measure the toxicity of LPS to the cells. Next, we used immunofluorescence to measure nuclear translocation of Nrf2 in PC12 cells. PC12 cells were then treated with IGF-1 (PI3K agonist) and LY294002 (PI3K inhibitor). An in-vitro model of SCI was then established via oxygen-glucose deprivation/reoxygenation. Rates of apoptosis were measured using flow cytometry and the TUNEL assay. Low-dose LPS increased the expression levels of Nrf2, p-PI3K/PI3K, and p-AKT/AKT, and facilitated nuclear translocation of Nrf2. The activation of PI3K-AKT signaling by IGF-1 significantly increased the expression of Nrf2, whereas inhibition of PI3K-AKT signaling significantly decreased the expression of Nrf2. Low-dose LPS reduced the apoptotic ratio of PC12 cells, decreased the expression levels of caspase 3 and caspase 9, and increased the expression levels of HO-1, NQO1, and γ-GCS. Low-dose LPS also reduced the rate of apoptosis and oxidative stress by activating the PI3K-AKT-Nrf2 signaling pathway. Collectively, the results indicate that PI3K-AKT-Nrf2 signaling participates in the protective effects from low-dose LPS in an in-vitro PC12 cell model of SCI.


Assuntos
Lipopolissacarídeos/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Neurônios/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Substâncias Protetoras/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Traumatismos da Medula Espinal/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Fator 2 Relacionado a NF-E2/genética , Neurônios/metabolismo , Células PC12 , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Ratos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/patologia
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