Abstract
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.
Original language | English |
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Pages (from-to) | 82-88 |
Number of pages | 7 |
Journal | Biochemical and biophysical research communications |
Volume | 590 |
DOIs | |
Publication status | Published - 2022 Jan 29 |
Keywords
- AMPK
- ATM
- DNA-PKcs
- Hypoxia
- Radiation
- Sp1
ASJC Scopus subject areas
- Biophysics
- Biochemistry
- Molecular Biology
- Cell Biology