Significance of the Wnt canonical pathway in radiotoxicity via oxidative stress of electron beam radiation and its molecular control in mice

Kumar, Shashank and Fathima, Eram and Khanum, Farhath and Malini, S. S. (2023) Significance of the Wnt canonical pathway in radiotoxicity via oxidative stress of electron beam radiation and its molecular control in mice. International Journal of Radiation Biology, 99 (3). pp. 459-473. ISSN 1362-3095

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Official URL: https://doi.org/10.1080/09553002.2022.2094018

Abstract

Purpose Radiation triggers cell death events through signaling proteins, but the combined mechanism of these events is unexplored The Wnt canonical pathway, on the other hand, is essential for cell regeneration and cell fate determination. Aim The relationship between the Wnt pathway's response to radiation and its role in radiotoxicity is overlooked, even though it is a critical molecular control of the cell. The Wnt pathway has been predicted to have radioprotective properties in some reports, but the overall mechanism is unknown. We intend to investigate how this combined cascade works throughout the radiation process and its significance over radiotoxicity. Materials and methods Thirty adult mice were irradiated with electron beam radiation, and 5 served as controls. Mice were sacrificed after 24 h and 30 days of irradiation. We assessed DNA damage studies, oxidative stress parameters, mRNA profiles, protein level (liver, kidney, spleen, and germ cells), sperm viability, and motility. Observation The mRNA profile helps to understand how the combined cascade of the Wnt pathway and NHEJ work together during radiation to combat oxidative response and cell survival. The quantitative examination of mRNA uncovers unique critical changes in all mRNA levels in all cases, particularly in germ cells. Recuperation was likewise seen in post-30 day's radiation in the liver, spleen, and kidney followed by oxidative stress parameters, however not in germ cells. It proposes that reproductive physiology is exceptionally sensitive to radiation, even at the molecular level. It also suggests the suppression of Lef1/Axin2 could be the main reason for the permanent failure of the sperm function process. Post-irradiation likewise influences the morphology of sperm. The decrease in mRNA levels of Lef1, Axin2, Survivin, Ku70, and XRCC6 levels suggests radiation inhibits the Wnt canonical pathway and failure in DNA repair mechanisms in a coupled manner. An increase in Bax, Bcl2, and caspase3 suggests apoptosis activation followed by the decreased expression of enzymatic antioxidants. Conclusion Controlled several interlinked such as the Wnt canonical pathway, NHEJ pathway, and intrinsic apoptotic pathway execute when the whole body is exposed to radiation. These pathways decide the cell fate whether it will survive or will go to apoptosis which may further be used in a study to counterpart and better comprehend medication focus on radiation treatment

Item Type: Article
Uncontrolled Keywords: Electron beam radiation; Wnt canonical pathway; apoptosis; oxidative stress; DNA damage; radio-toxicity
Subjects: B Life Science > Zoology
Divisions: Department of > Zoology
Depositing User: C Swapna Library Assistant
Date Deposited: 04 Sep 2023 09:34
Last Modified: 04 Sep 2023 09:34
URI: http://eprints.uni-mysore.ac.in/id/eprint/17713

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