Deinococcus Antioxidants are Extremely Radioprotective of Cultured Human Cells

The toxicity of ionizing radiation in diverse cell-types is associated with a high susceptibility to proteome oxidation, but not in extremely resistant bacteria such as Deinococcus radiodurans (DR). Mn2+-peptide antioxidant complexes accumulated in DR specifically protect proteins from reactive oxygen species (ROS) generated by radiation, preserving enzymatic functions needed to recover from genome damage. We previously reported that protein-free cell extracts of DR protected enzymes and human lymphoblastoid Jurkat T cells from extreme cellular insults caused by γ-rays. Here we show that the levels of radioprotection conferred on Jurkat cells by DR-based rationally-designed peptides far exceed the levels bestowed by D. radiodurans ultrafiltrate. The relative radioprotective efficacy of the peptides on the viability of irradiated Jurkat cells was determined by flow cytometry using SYTOX Blue dye that readily penetrates cells with compromised plasma membranes. The addition of 3 mM DEHGTAVMLK (DP1) as a radioprotector to RPMI medium pre- or post-irradiation increased the viability of Jurkat cells exposed to 100 Gy from ~20% to ~80-90%. The radioprotective efficacy of other designed peptides will be reported. Deinococcus Mn2+ antioxidant complexes could expand pre-exposure prophylactic countermeasures and post-exposure therapeutics in cancer radiotherapy and in radiation emergencies.