PERIOD 2 regulates low-dose radioprotection via PER2/pGSK3β/β-catenin/Per2 loop.

Autor:	Alexandrou AT; Department of Radiation Oncology, University of California at Davis, 4501 X Street, Sacramento, CA 95817, USA.; Department of Natural and Quantitative Sciences, Holy Cross College, Notre Dame, IN 46556, USA., Duan Y; Department of Radiation Oncology, University of California at Davis, 4501 X Street, Sacramento, CA 95817, USA., Xu S; Department of Surgery, School of Medicine, University of California at Davis, Sacramento, CA 95817, USA., Tepper C; Department of Biochemistry and Molecular Medicine, University of California at Davis, Sacramento, CA 95817, USA., Fan M; Department of Radiation Oncology, University of California at Davis, 4501 X Street, Sacramento, CA 95817, USA., Tang J; Department of Radiation Oncology, University of California at Davis, 4501 X Street, Sacramento, CA 95817, USA., Berg J; Department of Radiation Oncology, University of California at Davis, 4501 X Street, Sacramento, CA 95817, USA., Basheer W; Department of Radiation Oncology, University of California at Davis, 4501 X Street, Sacramento, CA 95817, USA., Valicenti T; Department of Radiation Oncology, University of California at Davis, 4501 X Street, Sacramento, CA 95817, USA., Wilson PF; Department of Radiation Oncology, University of California at Davis, 4501 X Street, Sacramento, CA 95817, USA., Coleman MA; Department of Radiation Oncology, University of California at Davis, 4501 X Street, Sacramento, CA 95817, USA., Vaughan AT; Department of Radiation Oncology, University of California at Davis, 4501 X Street, Sacramento, CA 95817, USA., Fu L; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA., Grdina DJ; Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL 60637, USA., Murley J; Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL 60637, USA., Wang A; Department of Surgery, School of Medicine, University of California at Davis, Sacramento, CA 95817, USA., Woloschak G; Department of Radiation Oncology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60637, USA., Li JJ; Department of Radiation Oncology, University of California at Davis, 4501 X Street, Sacramento, CA 95817, USA.; NCI-designated Comprehensive Cancer Center, University of California at Davis, 4501 X Street, Sacramento, CA 95817, USA.
Jazyk:	angličtina
Zdroj:	IScience [iScience] 2022 Nov 09; Vol. 25 (12), pp. 105546. Date of Electronic Publication: 2022 Nov 09 (Print Publication: 2022).
DOI:	10.1016/j.isci.2022.105546
Abstrakt:	During evolution, humans are acclimatized to the stresses of natural radiation and circadian rhythmicity. Radiosensitivity of mammalian cells varies in the circadian period and adaptive radioprotection can be induced by pre-exposure to low-level radiation (LDR). It is unclear, however, if clock proteins participate in signaling LDR radioprotection. Herein, we demonstrate that radiosensitivity is increased in mice with the deficient Period 2 gene (Per2 def ) due to impaired DNA repair and mitochondrial function in progenitor bone marrow hematopoietic stem cells and monocytes. Per2 induction and radioprotection are also identified in LDR-treated Per2 wt mouse cells and in human skin (HK18) and breast (MCF-10A) epithelial cells. LDR-boosted PER2 interacts with pGSK3β(S9) which activates β-catenin and the LEF/TCF mediated gene transcription including Per2 and genes involved in DNA repair and mitochondrial functions. This study demonstrates that PER2 plays an active role in LDR adaptive radioprotection via PER2/pGSK3β/β-catenin/Per2 loop, a potential target for protecting normal cells from radiation injury. Competing Interests: The authors declare no competing interests. (© 2022 The Author(s).)
Databáze:	MEDLINE
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