Melatonin Protects Against Hyperoxia-Induced Apoptosis in Alveolar Epithelial type II Cells by Activating the MT2/PI3K/AKT/ETS1 Signaling Pathway.
Infant, Newborn
Humans
Alveolar Epithelial Cells
Hyperoxia
/ metabolism
Proto-Oncogene Proteins c-akt
/ metabolism
Melatonin
/ pharmacology
Phosphatidylinositol 3-Kinases
/ metabolism
Receptors, Melatonin
/ metabolism
Signal Transduction
Apoptosis
Bronchopulmonary Dysplasia
/ metabolism
Epithelial Cells
/ metabolism
Proto-Oncogene Protein c-ets-1
Apoptosis
Bronchopulmonary dysplasia
ETS1
Lung injury
Melatonin
Melatonin receptors
Journal
Lung
ISSN: 1432-1750
Titre abrégé: Lung
Pays: United States
ID NLM: 7701875
Informations de publication
Date de publication:
04 2023
04 2023
Historique:
received:
30
12
2022
accepted:
02
03
2023
medline:
21
4
2023
pubmed:
18
3
2023
entrez:
17
3
2023
Statut:
ppublish
Résumé
Hyperoxia-induced apoptosis in alveolar epithelial type II cells (AECIIs) plays a critical role in the development of bronchopulmonary dysplasia (BPD). Melatonin has been shown to improve BPD. However, the protective effect of melatonin on hyperoxia-induced apoptosis in AECIIs and the precise mechanisms involved remain unclear. Human alveolar epithelial type II A549 cells were treated with hyperoxia as an in vitro model to investigate the antiapoptotic mechanism of melatonin. CCK-8 assays were performed to investigate the viability of A549 cells. Hoechst 33,258 staining was carried out to quantify apoptosis in A549 cells. The protein expression levels of E26 oncogene homolog 1 (ETS1), Bcl-2, Bax, Bim, Wnt, β-catenin, AKT and phosphorylated AKT were measured by western blotting. LY294002, SC79 and the downregulation of ETS1, melatonin receptor 1 (MT1) and MT2 with specific siRNAs were used to investigate the role of the PI3K/AKT pathway, ETS1, MT1 and MT2 in hyperoxia-induced apoptosis in A549 cells. Melatonin prevented hyperoxia-induced apoptosis in A549 cells, and the upregulation of E26 oncogene homolog 1 (ETS1) contributed to the antiapoptotic effect of melatonin. Melatonin activated the PI3K/AKT axis, which led to ETS1 upregulation and inhibited apoptosis in hyperoxia-exposed A549 cells. Furthermore, melatonin-induced activation of the PI3K/AKT axis, upregulation of ETS1 and inhibition of apoptosis were reversed by melatonin receptor 2 (MT2) siRNA in hyperoxia-exposed A549 cells. Melatonin prevents hyperoxia-induced apoptosis by activating the MT2/PI3K/AKT/ETS1 axis in alveolar epithelial cells.
Identifiants
pubmed: 36928143
doi: 10.1007/s00408-023-00610-0
pii: 10.1007/s00408-023-00610-0
doi:
Substances chimiques
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
Melatonin
JL5DK93RCL
Phosphatidylinositol 3-Kinases
EC 2.7.1.-
Receptors, Melatonin
0
ETS1 protein, human
0
Proto-Oncogene Protein c-ets-1
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
225-234Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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