Attenuation of PM2.5-induced alveolar epithelial cells and lung injury through regulation of mitochondrial fission and fusion.
Part Fibre Toxicol
; 20(1): 28, 2023 07 18.
Article
en En
| MEDLINE
| ID: mdl-37464447
ABSTRACT
BACKGROUND:
Exposure to particulate matter (PM) with an aerodynamic diameter less than 2.5 µm (PM2.5) is a risk factor for developing pulmonary diseases and the worsening of ongoing disease. Mitochondrial fission and fusion are essential processes underlying mitochondrial homeostasis in health and disease. We examined the role of mitochondrial fission and fusion in PM2.5-induced alveolar epithelial cell damage and lung injury. Key genes in these processes include dystrophin-related protein 1 (DRP1) and optic atrophy 1 (OPA1) respectively.METHODS:
Alveolar epithelial (A549) cells were treated with PM2.5 (32 µg/ml) in the presence and absence of Mdivi-1 (10µM, a DRP1 inhibitor) or BGP-15 (10µM, an OPA1 activator). Results were validated using DRP1-knockdown (KD) and OPA1-overexpression (OE). Mice were injected intraperitoneally with Mdivi-1 (20 mg/kg), BGP-15 (20 mg/kg) or distilled water (control) one hour before intranasal instillation of PM2.5 (7.8 mg/kg) or distilled water for two consecutive days.RESULTS:
PM2.5 exposure of A549 cells caused oxidative stress, enhanced inflammation, necroptosis, mitophagy and mitochondrial dysfunction indicated by abnormal mitochondrial morphology, decreased mitochondrial membrane potential (ΔΨm), reduced mitochondrial respiration and disrupted mitochondrial fission and fusion. Regulating mitochondrial fission and fusion pharmacologically using Mdivi-1 and BGP-15 and genetically using DRP1-KD and OPA1-OE prevented PM2.5-induced celluar damage in A549 cells. Mdivi-1 and BGP-15 attenuated PM2.5-induced acute lung injury in mice.CONCLUSION:
Increased mitochondrial fission and decreased mitochondrial fusion may underlie PM2.5-induced alveolar epithelial cell damage in vitro and lung injury in vivo.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Material Particulado
/
Lesión Pulmonar
Tipo de estudio:
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
Part Fibre Toxicol
Asunto de la revista:
TOXICOLOGIA
Año:
2023
Tipo del documento:
Article