Palmitate promotes autophagy and apoptosis through ROS-dependent JNK and p38 MAPK.
Biochem Biophys Res Commun
; 463(3): 262-7, 2015 Jul 31.
Article
em En
| MEDLINE
| ID: mdl-26002468
ABSTRACT
Palmitate (PA), one of the most prevalent saturated fatty acids, causes myocardial dysfunction. However, the mechanisms by which PA induces cell apoptosis and autophagy remain to be elucidated. We showed that autophagy was induced in an mTORC1-dependent way and played a protective role against PA-induced apoptosis, which was verified by pretreatment with 3-methyladenine (3MA) and rapamycin. However, p62 began to accumulate after 18 h treatment with PA, suggesting prolonged exposure to PA lead to an impairment of autophagic flux. PA enhanced ROS production as well as activated p38-mitogen-activated protein kinase (p38 MAPK) and c-jun NH2 terminal kinases (JNKs). The antioxidant N-Acety-l-Cysteine (NAC) was found to attenuate the JNK and p38 MAPK activation with a concomitant reduction of PA-induced autophagy and apoptosis. Furthermore, both JNK and p38 MAPK inhibitors were shown to directly abrogate caspase 7 cleavage as well as the conversion of LC3BI to LC3BII. Thus, we demonstrate that PA stimulates autophagy and apoptosis via ROS-dependent JNK and p38 MAPK pathways.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Palmitatos
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Autofagia
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Espécies Reativas de Oxigênio
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Proteínas Quinases JNK Ativadas por Mitógeno
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Proteínas Quinases p38 Ativadas por Mitógeno
Limite:
Animals
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article