AMPK increases expression of ATM through transcriptional factor Sp1 and induces radioresistance under severe hypoxia in glioblastoma cell lines.
AMP-Activated Protein Kinases
/ metabolism
Ataxia Telangiectasia Mutated Proteins
/ metabolism
Cell Cycle
Cell Line, Tumor
DNA-Activated Protein Kinase
/ metabolism
Forkhead Box Protein O3
/ metabolism
Gene Knockdown Techniques
Glioblastoma
/ pathology
Humans
Hypoxia-Inducible Factor 1, alpha Subunit
/ metabolism
Neoplasm Proteins
/ metabolism
Radiation Tolerance
Sp1 Transcription Factor
/ metabolism
Tumor Hypoxia
AMPK
ATM
DNA-PKcs
Hypoxia
Radiation
Sp1
Journal
Biochemical and biophysical research communications
ISSN: 1090-2104
Titre abrégé: Biochem Biophys Res Commun
Pays: United States
ID NLM: 0372516
Informations de publication
Date de publication:
29 01 2022
29 01 2022
Historique:
received:
21
12
2021
accepted:
21
12
2021
pubmed:
2
1
2022
medline:
11
2
2022
entrez:
1
1
2022
Statut:
ppublish
Résumé
We have previously reported that severe hypoxia increases expression and activity of the DNA damage sensor ATM by activation of the key energy sensor AMPK. Here, to elucidate molecular mechanisms underlying increased expression and activity of ATM by AMPK under severe hypoxia, we investigated roles of transcriptional factors Sp1 and FoxO3a using human glioblastoma cell lines T98G and A172. Severe hypoxia increased expression of ATM, AMPKα and Sp1 but not that of FoxO3a. Knockdown of AMPKα suppressed expression of ATM and Sp1 and suppressed cellular radioresistance under severe hypoxia without affecting cell cycle distribution. Knockdown of Sp1 suppressed expression of ATM. These results suggest that increased expression and activity of AMPK under severe hypoxia induce cellular radioresistance through AMPK/Sp1/ATM pathway.
Identifiants
pubmed: 34973534
pii: S0006-291X(21)01717-4
doi: 10.1016/j.bbrc.2021.12.076
pii:
doi:
Substances chimiques
FOXO3 protein, human
0
Forkhead Box Protein O3
0
HIF1A protein, human
0
Hypoxia-Inducible Factor 1, alpha Subunit
0
Neoplasm Proteins
0
Sp1 Transcription Factor
0
Ataxia Telangiectasia Mutated Proteins
EC 2.7.11.1
DNA-Activated Protein Kinase
EC 2.7.11.1
PRKDC protein, human
EC 2.7.11.1
AMP-Activated Protein Kinases
EC 2.7.11.31
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
82-88Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare no conflict of interest.