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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...

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Autores principales: Banerjee, Sudip, Shah, Sumit K., Melnyk, Stepan B., Pathak, Rupak, Hauer-Jensen, Martin, Pawar, Snehalata A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
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.
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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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