Banerjee Sudip, Shah Sumit K, Melnyk Stepan B, Pathak Rupak, Hauer-Jensen Martin, Pawar Snehalata A
Division of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Arkansas Children's Hospital Research Institute, Little Rock, AR 72205, USA.
Antioxidants (Basel). 2018 Apr 6;7(4):55. doi: 10.3390/antiox7040055.
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 () display increased mortality to IR due to injury to the hematopoietic and intestinal tissues and that protects from IR-induced oxidative stress and cell death. The purpose of this study was to investigate whether mediates the radio protective functions of GT3. We found that GT3-treated mice showed partial recovery of white blood cells compared to GT3-treated mice at 2 weeks post-IR. GT3-treated 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 mice. 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 and mice. These results identify a novel role for 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.
γ-生育三烯酚（GT3）可保护机体免受电离辐射（IR）诱导的损伤。然而，GT3发挥保护作用的分子靶点尚不清楚。我们曾报道，缺乏CCAAT增强子结合蛋白δ（）的小鼠因造血组织和肠道组织受损，对IR的死亡率增加，且 可保护机体免受IR诱导的氧化应激和细胞死亡。本研究旨在探讨 是否介导GT3的辐射防护功能。我们发现，与IR照射后2周的GT3处理的 小鼠相比，GT3处理的 小鼠白细胞有部分恢复。与GT3处理的 小鼠相比，GT3处理的 小鼠肠道隐窝集落损失增加，这与暴露于IR后炎症细胞因子和趋化因子表达增加、氧化型谷胱甘肽（GSSG）、S-亚硝基谷胱甘肽（GSNO）和3-硝基酪氨酸（3-NT）水平升高相关。 在肠道中可由IR以及IR与GT3的组合诱导产生。研究表明，粒细胞集落刺激因子（G-CSF）介导GT3的辐射防护功能。有趣的是，我们发现单独的IR以及IR与GT3的组合均可使 和 小鼠的血浆G-CSF显著增加。这些结果确定了 在GT3介导的抗IR诱导损伤保护中的新作用，部分是通过调节IR诱导的炎症和氧化/亚硝化应激实现的，且这一作用独立于G-CSF。
