Delta-Tocotrienol Suppresses Radiation-Induced MicroRNA-30 and Protects Mice and Human CD34+ Cells from Radiation Injury

Abstract

We reported that microRNA-30c (miR-30c) plays a key role in radiation-induced human cell damage through an apoptotic pathway. Herein we further evaluated radiation-induced miR-30 expression and mechanisms of delta-tocotrienol (DT3), a radiation countermeasure candidate, for regulating miR-30 in a mouse model and human hematopoietic CD34+ cells. CD2F1 mice were exposed to 0 (control) or 7-12.5 Gy total-body gamma-radiation, and CD34+ cells were irradiated with 0, 2 or 4 Gy of radiation. Single doses of DT3 (75 mg/kg, subcutaneous injection for mice or 2 μM for CD34+ cell culture) were administrated 24 h before irradiation and animal survival was monitored for 30 days. Mouse bone marrow (BM), jejunum, kidney, liver and serum as well as CD34+ cells were collected at 1, 4, 8, 24, 48 or 72 h after irradiation to determine apoptotic markers, pro-inflammatory cytokines interleukin (IL)-1β and IL-6, miR-30, and stress response protein expression. Our results showed that radiation-induced IL-1β release and cell damage are pathological states that lead to an early expression and secretion of miR-30b and miR-30c in mouse tissues and serum and in human CD34+ cells. DT3 suppressed IL-1β and miR-30 expression, protected against radiation-induced apoptosis in mouse and human cells, and increased survival of irradiated mice. Furthermore, an anti-IL-1β antibody downregulated radiation-induced NFκBp65 phosphorylation, inhibited miR-30 expression and protected CD34+ cells from radiation exposure. Knockdown of NFκBp65 by small interfering RNA (siRNA) significantly suppressed radiation-induced miR-30 expression in CD34+ cells. Our data suggest that DT3 protects human and mouse cells from radiation damage may through suppression of IL-1β-induced NFκB/miR-30 signaling.

DOI: 10.1371/journal.pone.0122258

Extracted Key Phrases

7 Figures and Tables

050100201520162017
Citations per Year

Citation Velocity: 13

Averaging 13 citations per year over the last 3 years.

Learn more about how we calculate this metric in our FAQ.

Cite this paper

@inproceedings{Li2015DeltaTocotrienolSR, title={Delta-Tocotrienol Suppresses Radiation-Induced MicroRNA-30 and Protects Mice and Human CD34+ Cells from Radiation Injury}, author={Xiang Li and Cam T. Ha and Dadin Fu and Michael R. Landauer and Sanchita P. Ghosh and Mang Xiao}, booktitle={PloS one}, year={2015} }