Inhibition of mitochondrial autophagy protects donor lungs for lung transplantation against ischaemia-reperfusion injury in rats via the mTOR pathway.
J Cell Mol Med
; 23(5): 3190-3201, 2019 05.
Article
en En
| MEDLINE
| ID: mdl-30887674
ABSTRACT
Impaired mitochondrial function is a key factor attributing to lung ischaemia-reperfusion (IR) injury, which contributes to major post-transplant complications. Thus, the current study was performed to investigate the role of mitochondrial autophagy in lung I/R injury and the involvement of the mTOR pathway. We established rat models of orthotopic left lung transplantation to investigate the role of mitochondrial autophagy in I/R injury following lung transplantation. Next, we treated the donor lungs with 3-MA and Rapamycin to evaluate mitochondrial autophagy, lung function and cell apoptosis with different time intervals of cold ischaemia preservation and reperfusion. In addition, mitochondrial autophagy, and cell proliferation and apoptosis of pulmonary microvascular endothelial cells (PMVECs) exposed to hypoxia-reoxygenation (H/R) were monitored after 3-MA administration or Rapamycin treatment. The cell apoptosis could be inhibited by mitochondrial autophagy at the beginning of lung ischaemia, but was rendered out of control when mitochondrial autophagy reached normal levels. After I/R of donor lung, the mitochondrial autophagy was increased until 6 hours after reperfusion and then gradually decreased. The elevation of mitochondrial autophagy was accompanied by promoted apoptosis, aggravated lung injury and deteriorated lung function. Moreover, the suppression of mitochondrial autophagy by 3-MA inhibited cell apoptosis of donor lung to alleviate I/R-induced lung injury as well as inhibited H/R-induced PMVEC apoptosis, and enhanced its proliferation. Finally, mTOR pathway participated in I/R- and H/R-mediated mitochondrial autophagy in regulation of cell apoptosis. Inhibition of I/R-induced mitochondrial autophagy alleviated lung injury via the mTOR pathway, suggesting a potential therapeutic strategy for lung I/R injury.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Autofagia
/
Daño por Reperfusión
/
Serina-Treonina Quinasas TOR
/
Mitocondrias
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Cell Mol Med
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2019
Tipo del documento:
Article