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Cebpd Is Essential for Gamma-Tocotrienol Mediated Protection against Radiation-Induced Hematopoietic and Intestinal Injury
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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5946121/ https://www.ncbi.nlm.nih.gov/pubmed/29642403 http://dx.doi.org/10.3390/antiox7040055 |
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author | Banerjee, Sudip Shah, Sumit K. Melnyk, Stepan B. Pathak, Rupak Hauer-Jensen, Martin Pawar, Snehalata A. |
author_facet | Banerjee, Sudip Shah, Sumit K. Melnyk, Stepan B. Pathak, Rupak Hauer-Jensen, Martin Pawar, Snehalata A. |
author_sort | Banerjee, Sudip |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5946121 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-59461212018-05-15 Cebpd Is Essential for Gamma-Tocotrienol Mediated Protection against Radiation-Induced Hematopoietic and Intestinal Injury Banerjee, Sudip Shah, Sumit K. Melnyk, Stepan B. Pathak, Rupak Hauer-Jensen, Martin Pawar, Snehalata A. Antioxidants (Basel) Article 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. MDPI 2018-04-06 /pmc/articles/PMC5946121/ /pubmed/29642403 http://dx.doi.org/10.3390/antiox7040055 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Banerjee, Sudip Shah, Sumit K. Melnyk, Stepan B. Pathak, Rupak Hauer-Jensen, Martin Pawar, Snehalata A. Cebpd Is Essential for Gamma-Tocotrienol Mediated Protection against Radiation-Induced Hematopoietic and Intestinal Injury |
title | Cebpd Is Essential for Gamma-Tocotrienol Mediated Protection against Radiation-Induced Hematopoietic and Intestinal Injury |
title_full | Cebpd Is Essential for Gamma-Tocotrienol Mediated Protection against Radiation-Induced Hematopoietic and Intestinal Injury |
title_fullStr | Cebpd Is Essential for Gamma-Tocotrienol Mediated Protection against Radiation-Induced Hematopoietic and Intestinal Injury |
title_full_unstemmed | Cebpd Is Essential for Gamma-Tocotrienol Mediated Protection against Radiation-Induced Hematopoietic and Intestinal Injury |
title_short | Cebpd Is Essential for Gamma-Tocotrienol Mediated Protection against Radiation-Induced Hematopoietic and Intestinal Injury |
title_sort | cebpd is essential for gamma-tocotrienol mediated protection against radiation-induced hematopoietic and intestinal injury |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5946121/ https://www.ncbi.nlm.nih.gov/pubmed/29642403 http://dx.doi.org/10.3390/antiox7040055 |
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