Polydatin mediates Parkin-dependent mitophagy and protects against mitochondria-dependent apoptosis in acute respiratory distress syndrome.
Lab Invest
; 99(6): 819-829, 2019 06.
Article
em En
| MEDLINE
| ID: mdl-30808930
ABSTRACT
Mitophagy removes dysfunctional mitochondria and is known to play an important role in the pathogenesis of several diseases; however, the role of mitophagy in acute respiratory distress syndrome (ARDS) remains poorly understood. While we have previously demonstrated that polydatin (PD) improves lipopolysaccharide (LPS)-induced ARDS, the specific mechanism remains unclear. In present study, we aimed to determine whether PD activates Parkin-dependent mitophagy to protect against LPS-induced mitochondria-dependent apoptosis and lung injury. To establish the ARDS model, C57BL/6 mice were intratracheally injected with LPS (5 mg/kg) in vivo and Beas-2B cells were exposured to 0.5 mM LPS in vitro. Our results indicate that PD facilitates Parkin translocation to mitochondria and promotes mitophagy in ARDS-challenged mice and LPS-treated Beas-2B cells. However, PD-induced mitophagy was suppressed in Parkin-/- mice and Parkin siRNA transfected cells, indicating that PD activates Parkin-dependent mitophagy. Furthermore, the protective effects of PD against LPS-induced mitochondria-dependent apoptosis and lung injury were suppressed when Parkin was depleted both in vivo and in vitro. The inhibition of mitophagy with mitophagy inhibitor mitochondrial division inhibitor-1 in vivo and silencing of autophagy-related gene 7 in vitro also blocked the protective effects mediated by PD. Our data suggest that Parkin-dependent mitophagy induced by PD provides protection against mitochondria-dependent apoptosis in ARDS.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Síndrome do Desconforto Respiratório
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Estilbenos
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Apoptose
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Ubiquitina-Proteína Ligases
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Mitofagia
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Glucosídeos
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article