Sirtuin3 Alleviated Influenza A Virus-Induced Mitochondrial Oxidative Stress and Inflammation in Lung Epithelial Cells via Regulating Poly (ADP-Ribose) Polymerase 1 Activity.
Int Arch Allergy Immunol
; 184(5): 447-459, 2023.
Article
em En
| MEDLINE
| ID: mdl-36657406
ABSTRACT
INTRODUCTION:
Influenza A virus (IAV) infection causes severe lung inflammation and injury, particularly in children. Sirtuin3 (Sirt3) was confirmed to be effective in protecting the lung against injury. This study aims to explore the function and mechanism of Sirt3 on influenza development in children.METHODS:
The Sirt3 level in serum samples from IAV-infected children and lung epithelial cells were detected using RT-qPCR, ELISA, and Western blot assays. Cell viability and apoptosis were determined by MTT and flow cytometry assays. Virus titration was conducted by determining TCID50. Cell inflammatory response was detected by a battery of inflammatory cytokines. The contents of ROS and ATP, mitochondrial membrane potential level, and oxygen-consumption rate were examined to reflect on oxidative stress and mitochondrial dysfunction. The activity of poly (ADP-ribose) polymerase 1 (PARP-1) was measured by colorimetry.RESULTS:
Sirt3 was downregulated in IAV-infected children's serum samples and BEAS-2B cells. Overexpression of Sirt3 alleviated IAV replication and IAV-induced inflammatory injury, oxidative stress, and mitochondrial dysfunction in lung epithelial cells. Moreover, upregulation of Sirt3 deacetylated SOD2 and PARP-1 and inhibited the PARP-1 activity. Notably, the Sirt3 inhibitor (3-TYP) and PARP-1 activity agonist (nicotinamide) reversed the effects of Sirt3 overexpression on IAV replication and IAV-induced injury.CONCLUSION:
Overexpression of Sirt3 attenuated IAV-evoked inflammatory injury and mitochondrial oxidative stress through the inhibition of PARP-1 activity in lung epithelial cells.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vírus da Influenza A
/
Influenza Humana
/
Sirtuína 3
Limite:
Child
/
Humans
Idioma:
En
Revista:
Int Arch Allergy Immunol
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China