-tocotrienol protects mouse and human hematopoietic progenitors from  -irradiation through extracellular signal-regulated kinase/mammalian target of rapamycin signaling

作者：Xiaodong Li, Da-Qi Fu, Nursyani Latif, Conor Mullaney, Patrick H. Ney, Steven Mog, Mark H. Whitnall, V. Srinivasan, Mang Xiao · 发表于：Haematologica · 年份：2010 · DOI：10.3324/haematol.2010.026492 · 被引用次数：63 · 研究领域：Effects of Radiation Exposure、Antioxidant Activity and Oxidative Stress、Carcinogens and Genotoxicity Assessment

BACKGROUND: Exposure to γ-radiation causes rapid hematopoietic cell apoptosis and bone marrow suppression. However, there are no approved radiation countermeasures for the acute radiation syndrome. In this study, we demonstrated that natural δ-tocotrienol, one of the isomers of vitamin E, significantly enhanced survival in total body lethally irradiated mice. We explored the effects and mechanisms of δ-tocotrienol on hematopoietic progenitor cell survival after γ-irradiation in both in vivo and in vitro experiments. DESIGN AND METHODS: CD2F1 mice and human hematopoietic progenitor CD34(+) cells were treated with δ-tocotrienol or vehicle control 24 h before or 6 h after γ-irradiation. Effects of δ-tocotrienol on hematopoietic progenitor cell survival and regeneration were evaluated by clonogenicity studies, flow cytometry, and bone marrow histochemical staining. δ-tocotrienol and γ-irradiation-induced signal regulatory activities were assessed by immunofluorescence staining, immunoblotting and short-interfering RNA assay. RESULTS: δ-tocotrienol displayed significant radioprotective effects. A single injection of δ-tocotrienol protected 100% of CD2F1 mice from total body irradiation-induced death as measured by 30-day post-irradiation survival. δ-tocotrienol increased cell survival, and regeneration of hematopoietic microfoci and lineage(-)/Sca-1(+)/ckit(+) stem and progenitor cells in irradiated mouse bone marrow, and protected human CD34(+) cells from radiation-induced damage...