Glutamine maintains the stability of alveolar structure and function after lung transplantation by inhibiting autophagy.
Biochem Biophys Res Commun
; 727: 150308, 2024 Oct 01.
Article
en En
| MEDLINE
| ID: mdl-38968769
ABSTRACT
Excessive autophagy may lead to degradation and damage of alveolar epithelial cells after lung transplantation, eventually leading to alveolar epithelial cell loss, affecting the structural integrity and function of alveoli. Glutamine (Gln), a nutritional supplement, regulates autophagy through multiple signaling pathways. In this study, we explored the protective role of Gln on alveolar epithelial cells by inhibiting autophagy. In vivo, a rat orthotopic lung transplant model was carried out to evaluate the therapeutic effect of glutamine. Ischemia/reperfusion (I/R) induced alveolar collapse, edema, epithelial cell apoptosis, and inflammation, which led to a reduction of alveolar physiological function, such as an increase in peak airway pressure, and a decrease in lung compliance and oxygenation index. In comparison, Gln preserved alveolar structure and function by reducing alveolar apoptosis, inflammation, and edema. In vitro, a hypoxia/reoxygenation (H/R) cell model was performed to simulate IR injury on mouse lung epithelial (MLE) cells and human lung bronchus epithelial (Beas-2B) cells. H/R impaired the proliferation of epithelial cells and triggered cell apoptosis. In contrast, Gln normalized cell proliferation and suppressed I/R-induced cell apoptosis. The activation of mTOR and the downregulation of autophagy-related proteins (LC3, Atg5, Beclin1) were observed in Gln-treated lung tissues and alveolar epithelial cells. Both in vivo and in vitro, rapamycin, a classical mTOR inhibitor, reversed the beneficial effects of Gln on alveolar structure and function. Taken together, Glnpreserved alveolar structure and function after lung transplantation by inhibiting autophagy.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Alveolos Pulmonares
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Autofagia
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Daño por Reperfusión
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Trasplante de Pulmón
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Ratas Sprague-Dawley
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Glutamina
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2024
Tipo del documento:
Article