Simultaneous inactivation of GSK-3ß suppresses quercetin-induced apoptosis by inhibiting the JNK pathway.
Am J Physiol Lung Cell Mol Physiol
; 304(11): L782-9, 2013 Jun 01.
Article
em En
| MEDLINE
| ID: mdl-23564507
ABSTRACT
Quercetin, a ubiquitous bioactive plant flavonoid, has shown to exert a broad range of activities, such as apoptotic, antioxidant, and anti-inflammatory effects. Thus, flavonoids can mediate both cell protection and cell injury. Recently, quercetin has been reported to prevent the progression of emphysema in animal models through antioxidant and anti-inflammatory actions. These findings suggest that quercetin could be a potential treatment option for chronic obstructive pulmonary disease. Its clinical application, however, could be limited by the cytotoxicity of quercetin, and understanding of the apoptotic mechanisms of quercetin is a prerequisite to develop a therapeutic strategy with minimal cytotoxicity. We evaluated the apoptotic effect of quercetin and its molecular mechanisms in normal bronchial epithelial cells (BEAS-2B cells). Quercetin decreased the viability of BEAS-2B cells via apoptosis in a dose- and time-dependent manner. Quercetin activated JNK and increased the expression levels of c-Jun and p53-dependent Bax. Blockade of JNK activation by overexpression of dominant negative JNK1 suppressed apoptosis by quercetin via inhibition of caspase-3 activation and reduction of p53 and Bax expression. Simultaneously, quercetin inactivated glycogen synthase kinase (GSK)-3ß, which is phosphatidylinositol 3-kinase/Akt dependent. Overexpression of a constitutively active GSK-3ß mutant enhanced quercetin-induced JNK activation. In contrast, overexpression of enzymatically inert GSK-3ß inhibited JNK activation, resulting in a suppression of apoptosis by quercetin. Taken together, the JNK-p53 pathway is involved in quercetin-induced apoptosis, and simultaneous inactivation of GSK-3ß can attenuate apoptosis in normal bronchial epithelial cells.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Quercetina
/
Apoptose
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Sistema de Sinalização das MAP Quinases
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Quinase 3 da Glicogênio Sintase
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article