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Antioxidants 2018, 7(4), 55; https://doi.org/10.3390/antiox7040055

Cebpd Is Essential for Gamma-Tocotrienol Mediated Protection against Radiation-Induced Hematopoietic and Intestinal Injury

1
Division of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
2
Arkansas Children’s Hospital Research Institute, Little Rock, AR 72205, USA
*
Author to whom correspondence should be addressed.
Received: 6 March 2018 / Revised: 2 April 2018 / Accepted: 3 April 2018 / Published: 6 April 2018
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Abstract

Gamma-tocotrienol (GT3) confers protection against ionizing radiation (IR)-induced injury. However, the molecular targets that underlie the protective functions of GT3 are not yet known. We have reported that mice lacking CCAAT enhancer binding protein delta (Cebpd−/−) display increased mortality to IR due to injury to the hematopoietic and intestinal tissues and that Cebpd protects from IR-induced oxidative stress and cell death. The purpose of this study was to investigate whether Cebpd mediates the radio protective functions of GT3. We found that GT3-treated Cebpd−/− mice showed partial recovery of white blood cells compared to GT3-treated Cebpd+/+ mice at 2 weeks post-IR. GT3-treated Cebpd−/− mice showed an increased loss of intestinal crypt colonies, which correlated with increased expression of inflammatory cytokines and chemokines, increased levels of oxidized glutathione (GSSG), S-nitrosoglutathione (GSNO) and 3-nitrotyrosine (3-NT) after exposure to IR compared to GT3-treated Cebpd+/+ mice. Cebpd is induced by IR as well as a combination of IR and GT3 in the intestine. Studies have shown that granulocyte-colony stimulating factor (G-CSF), mediates the radioprotective functions of GT3. Interestingly, we found that IR alone as well as the combination of IR and GT3 caused robust augmentation of plasma G-CSF in both Cebpd+/+ and Cebpd−/− mice. These results identify a novel role for Cebpd in GT3-mediated protection against IR-induced injury, in part via modulation of IR-induced inflammation and oxidative/nitrosative stress, which is independent of G-CSF. View Full-Text
Keywords: Cebpd; gamma tocotrienol; granulocyte-colony stimulating factor; intestinal injury; hematopoietic injury; ionizing radiation; GSNO; GSH Cebpd; gamma tocotrienol; granulocyte-colony stimulating factor; intestinal injury; hematopoietic injury; ionizing radiation; GSNO; GSH
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Banerjee, S.; Shah, S.K.; Melnyk, S.B.; Pathak, R.; Hauer-Jensen, M.; Pawar, S.A. Cebpd Is Essential for Gamma-Tocotrienol Mediated Protection against Radiation-Induced Hematopoietic and Intestinal Injury. Antioxidants 2018, 7, 55.

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