Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 590, Issue -, Pages 82-88Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2021.12.076
Keywords
Hypoxia; AMPK; Sp1; ATM; DNA-PKcs; Radiation
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Funding
- Ministry of Education, Culture, Sports, Science and Technology of Japan [19K17222, 17H06528]
- Grants-in-Aid for Scientific Research [19K17222, 17H06528] Funding Source: KAKEN
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Under severe hypoxia, AMPK increases ATM expression and activity through the AMPK/Sp1/ATM pathway, leading to enhanced cellular resistance to radiation.
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, AMPK alpha and Sp1 but not that of FoxO3a. Knockdown of AMPK alpha 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. (C) 2021 Elsevier Inc. All rights reserved.
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