Death-Associated Protein Kinase 1 Promotes Alveolar Epithelial Cell Apoptosis and Ventilator-Induced Lung Injury Through P53 Pathway.
Shock
; 57(1): 140-150, 2022 01 01.
Article
in En
| MEDLINE
| ID: mdl-34265832
ABSTRACT
OBJECTIVES:
Mechanical stretch-induced alveolar epithelial cell (AEC) apoptosis participates in the onset of ventilator-induced lung injury (VILI). In this study, we explored whether death-associated protein kinase 1 (DAPK1) mediated cyclic stretch (CS)-induced AEC apoptosis and VILI though P53 pathway. MATERIALS ANDMETHODS:
AEC apoptosis was induced by CS using the FX-5000T Flexercell Tension Plus system. C57BL/6 mouse received high tidal volume ventilation to build VILI model. DAPK1 inhibitor, P53 inhibitor, or DAPK1 plasmid was used to regulate the expression of DAPK1 and P53, respectively. Flow cytometery was performed to assay cell apoptosis and the changes of mitochondrial membrane potential (MMP); immunoblotting was adopted to analyze related protein expression. The binding of related proteins was detected by coimmunoprecipitation; AEC apoptosis in vivo was determined by immunohistochemistry assay.RESULTS:
CS promoted AEC apoptosis, increased DAPK1 and P53 expression, and induced the binding of DAPK1 and P53; inhibition of DAPK1 or P53 reduced CS-induced AEC apoptosis, suppressed the expression of Bax, increased Bcl-2 level, and stabilized MMP; AEC apoptosis and the level of P53 were both increased after overexpressing of DAPK1. Moreover, DAPK1 plasmid transfection also promoted the expression of Bax and the change of MMP, but decreased the level of Bcl-2. Inhibition of DAPK1 or P53 in vivo alleviated high tidal volume ventilation-induced AEC apoptosis and lung injury.CONCLUSIONS:
DAPK1 contributes to AEC apoptosis and the onset of VILI though P53 and its intrinsic pro-apoptotic pathway. Inhibition of DAPK1 or P53 alleviates high tidal volume ventilation-induced lung injury and AEC apoptosis.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Tumor Suppressor Protein p53
/
Ventilator-Induced Lung Injury
/
Alveolar Epithelial Cells
/
Death-Associated Protein Kinases
Type of study:
Risk_factors_studies
Limits:
Animals
Language:
En
Journal:
Shock
Journal subject:
ANGIOLOGIA
/
CARDIOLOGIA
Year:
2022
Document type:
Article
Affiliation country: