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Eur Rev Med Pharmacol Sci ; 22(7): 2015-2021, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29687857

RESUMO

OBJECTIVE: In Alzheimer's disease (AD), astrocytes are generally found in the surrounding of senile plaques participating in the production of phagocytosis and the removal of toxic compounds such as Aß. This study aimed at investigating the effect of Aß1-42 on astrocytes. MATERIALS AND METHODS: Cellular viability of primary cultured astrocytes was analyzed using CCK-8 assay. Quantitative Real-time PCR was used to assess the mRNA expression of JNK and AP-1. The proteins of JNK/AP-1 pathway were investigated using Western blot. RESULTS: Our findings showed that Aß1-42 inhibited cell viability and promoted apoptosis in astrocytes in primary culture. Additionally, Aß1-42 increased the mRNA expression level of AP-1, but had no effect on the expression of JNK. Furthermore, Aß1-42 increased the protein expression of p-JNK, p-c-jun and Fra-1 and the ratio of p-c-jun/c-jun and p-JNK/JNK. CONCLUSIONS: We showed that Aß1-42 promoted cell apoptosis in astrocytes in primary culture. Furthermore, Aß1-42 activated JNK/AP-1 pathway through promoting the phosphorylation of JNK, c-jun and Fra-1 expression, then inducing cell apoptosis.


Assuntos
Peptídeos beta-Amiloides/farmacologia , Astrócitos/efeitos dos fármacos , Proteínas Quinases JNK Ativadas por Mitógeno/fisiologia , Fragmentos de Peptídeos/farmacologia , Fator de Transcrição AP-1/fisiologia , Astrócitos/metabolismo , Células Cultivadas , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-fos/metabolismo , Transdução de Sinais/efeitos dos fármacos
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