期刊
ANTIOXIDANTS
卷 7, 期 4, 页码 -出版社
MDPI
DOI: 10.3390/antiox7040055
关键词
Cebpd; gamma tocotrienol; granulocyte-colony stimulating factor; intestinal injury; hematopoietic injury; ionizing radiation; GSNO; GSH
资金
- Center for Host Responses to Cancer therapy COBRE Grant [P20GM109005]
- Department of Defense [W81XWH-15-1-0489]
- Arkansas Bioscience Institute
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [P20GM109005] Funding Source: NIH RePORTER
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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