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Impairment of IGF-1 Signaling and Antioxidant Response Are Associated with Radiation Sensitivity and Mortality

Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD 20889, USA
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Int. J. Mol. Sci. 2021, 22(1), 451; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22010451
Received: 2 December 2020 / Revised: 19 December 2020 / Accepted: 29 December 2020 / Published: 5 January 2021
(This article belongs to the Section Molecular Toxicology)
Following exposure to high doses of ionizing radiation, diverse strains of vertebrate species will manifest varying levels of radiation sensitivity. To understand the inter-strain cellular and molecular mechanisms of radiation sensitivity, two mouse strains with varying radiosensitivity (C3H/HeN, and CD2F1), were exposed to total body irradiation (TBI). Since Insulin-like Growth Factor-1 (IGF-1) signaling pathway is associated with radiosensitivity, we investigated the link between systemic or tissue-specific IGF-1 signaling and radiosensitivity. Adult male C3H/HeN and CD2F1 mice were irradiated using gamma photons at Lethal Dose-70/30 (LD70/30), 7.8 and 9.35 Gy doses, respectively. Those mice that survived up to 30 days post-irradiation, were termed the survivors. Mice that were euthanized prior to 30 days post-irradiation due to deteriorated health were termed decedents. The analysis of non-irradiated and irradiated survivor and decedent mice showed that inter-strain radiosensitivity and post-irradiation survival outcomes are associated with activation status of tissue and systemic IGF-1 signaling, nuclear factor erythroid 2–related factor 2 (Nrf2) activation, and the gene expression profile of cardiac mitochondrial energy metabolism pathways. Our findings link radiosensitivity with dysregulation of IGF-1 signaling, and highlight the role of antioxidant gene response and mitochondrial function in radiation sensitivity. View Full-Text
Keywords: radiation injury; IGF-1; mitochondria; Nrf2; oxidative stress radiation injury; IGF-1; mitochondria; Nrf2; oxidative stress
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MDPI and ACS Style

Y. Aghdam, S.; Kenchegowda, D.; Holmes-Hampton, G.P.; Moroni, M.; P. Ghosh, S. Impairment of IGF-1 Signaling and Antioxidant Response Are Associated with Radiation Sensitivity and Mortality. Int. J. Mol. Sci. 2021, 22, 451. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22010451

AMA Style

Y. Aghdam S, Kenchegowda D, Holmes-Hampton GP, Moroni M, P. Ghosh S. Impairment of IGF-1 Signaling and Antioxidant Response Are Associated with Radiation Sensitivity and Mortality. International Journal of Molecular Sciences. 2021; 22(1):451. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22010451

Chicago/Turabian Style

Y. Aghdam, Saeed, Doreswamy Kenchegowda, Gregory P. Holmes-Hampton, Maria Moroni, and Sanchita P. Ghosh. 2021. "Impairment of IGF-1 Signaling and Antioxidant Response Are Associated with Radiation Sensitivity and Mortality" International Journal of Molecular Sciences 22, no. 1: 451. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22010451

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