Melatonin alleviates alcoholic liver disease
Alcoholic liver disease
BRG1
Binding receptor
Biophysics
EGFR
Melatonin
Safety
TERT
Journal
Acta pharmaceutica Sinica. B
ISSN: 2211-3835
Titre abrégé: Acta Pharm Sin B
Pays: Netherlands
ID NLM: 101600560
Informations de publication
Date de publication:
Jan 2023
Jan 2023
Historique:
received:
23
02
2022
revised:
24
04
2022
accepted:
12
05
2022
entrez:
23
2
2023
pubmed:
24
2
2023
medline:
24
2
2023
Statut:
ppublish
Résumé
Chronic alcohol consumption causes liver steatosis, cell death, and inflammation. Melatonin (MLT) is reported to alleviate alcoholic liver disease (ALD)-induced injury. However, its direct regulating targets in hepatocytes are not fully understood. In the current study, a cell-based screening model and a chronic ethanol-fed mice ALD model were used to test the protective mechanisms of MLT. MLT ameliorated ethanol-induced hepatocyte injury in both cell and animal models (optimal doses of 10 μmol/L and 5 mg/kg, respectively), including lowered liver steatosis, cell death, and inflammation. RNA-seq analysis and loss-of-function studies in AML-12 cells revealed that telomerase reverse transcriptase (TERT) was a key downstream effector of MLT. Biophysical assay found that epidermal growth factor receptor (EGFR) on the hepatocyte surface was a direct binding and regulating target of MLT. Liver specific knock-down of
Identifiants
pubmed: 36815038
doi: 10.1016/j.apsb.2022.06.015
pii: S2211-3835(22)00294-5
pmc: PMC9939303
doi:
Types de publication
Journal Article
Langues
eng
Pagination
100-112Informations de copyright
© 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.
Déclaration de conflit d'intérêts
The authors declare no conflicts of interest.
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