Restoration of autophagy by puerarin in lead-exposed primary rat proximal tubular cells via regulating AMPK-mTOR signaling.
J Biochem Mol Toxicol
; 31(3)2017 Mar.
Article
em En
| MEDLINE
| ID: mdl-27762461
ABSTRACT
Previous study has demonstrated that puerarin (PU) exerts nephroprotective effect against Pb-induced cytotoxicity in primary rat proximal tubular (rPT) cells. Autophagy can protect cells from various cytotoxic stimuli, but its role in the process of PU against Pb-induced nephrotoxicity is still unknown. This study aims to investigate whether PU can alleviate Pb-induced renal damage by recovering autophagy. Data showed that Pb inhibited the autophagic flux, as evidenced by the accumulation of LC3-II and p62 as well as the confocal microscopy analysis of GFP-LC3 puncta and punctate spots of monodansylcadaverine staining, whereas coadministration of PU could restore Pb-induced autophagy inhibition. Moreover, PU dramatically enhanced the phosphorylation of 5'AMP-activated protein kinase (AMPK) and inhibited the phosphorylation of mammalian target of rapamycin (mTOR) and its target proteins p70S6 kinase (p70S6K) and 4E-binding protein 1 (4E-BP1) in Pb-exposed rPT cells. Collectively, these evidence suggested that PU restored the impaired autophagic flux in Pb-treated rPT cells partly by activating autophagy via AMPK/mTOR-mediated signaling pathway.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Quinases Ativadas por AMP
/
Serina-Treonina Quinases TOR
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Isoflavonas
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Túbulos Renais Proximais
Limite:
Animals
Idioma:
En
Revista:
J Biochem Mol Toxicol
Assunto da revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
/
TOXICOLOGIA
Ano de publicação:
2017
Tipo de documento:
Article