title: MDP: A Deinococcus Mn2+-Decapeptide Complex Protects Mice from Ionizing Radiation.
abstract: The radioprotective capacity of a rationally-designed Mn2+-decapeptide complex (MDP), based on Mn antioxidants in the bacterium Deinococcus radiodurans, was investigated in a mouse model of radiation injury. MDP was previously reported to be extraordinarily radioprotective of proteins in the setting of vaccine development. The peptide-component (DEHGTAVMLK) of MDP applied here was selected from a group of synthetic peptides screened in vitro for their ability to protect cultured human cells and purified enzymes from extreme damage caused by ionizing radiation (IR). We show that the peptides accumulated in Jurkat T-cells and protected them from 100 Gy. MDP preserved the activity of T4 DNA ligase exposed to 60,000 Gy. In vivo, MDP was nontoxic and protected B6D2F1/J (female) mice from acute radiation syndrome. All irradiated mice treated with MDP survived exposure to 9.5 Gy (LD70/30) in comparison to the untreated mice, which displayed 63% lethality after 30 days. Our results show that MDP provides early protection of white blood cells, and attenuates IR-induced damage to bone marrow and hematopoietic stem cells via G-CSF and GM-CSF modulation. Moreover, MDP mediated the immunomodulation of several cytokine concentrations in serum including G-CSF, GM-CSF, IL-3 and IL-10 during early recovery. Our results present the necessary prelude for future efforts towards clinical application of MDP as a promising IR countermeasure. Further investigation of MDP as a pre-exposure prophylactic and post-exposure therapeutic in radiotherapy and radiation emergencies is warranted.
authors: Department of Pathology, Uniformed Services University of the Health Sciences (USUHS), School of Medicine, Bethesda, Maryland, United States of America.
authors: Paridhi
authors: P
authors: Gupta
authors: Department of Pathology, Uniformed Services University of the Health Sciences (USUHS), School of Medicine, Bethesda, Maryland, United States of America.|Biological Sciences Group, Birla Institute of Technology and Science, Pilani, Rajasthan, India.
authors: Manoshi
authors: M
authors: Gayen
authors: Radiation Combined Injury Program, Armed Forces Radiobiology Research Institute (AFRRI), Bethesda, Maryland, United States of America.
authors: Joan T
authors: JT
authors: Smith
authors: Department of Pathology, Uniformed Services University of the Health Sciences (USUHS), School of Medicine, Bethesda, Maryland, United States of America.
authors: Elena K
authors: EK
authors: Gaidamakova
authors: Department of Pathology, Uniformed Services University of the Health Sciences (USUHS), School of Medicine, Bethesda, Maryland, United States of America.
authors: Vera Y
authors: VY
authors: Matrosova
authors: Department of Pathology, Uniformed Services University of the Health Sciences (USUHS), School of Medicine, Bethesda, Maryland, United States of America.
authors: Olga
authors: O
authors: Grichenko
authors: Department of Pathology, Uniformed Services University of the Health Sciences (USUHS), School of Medicine, Bethesda, Maryland, United States of America.
authors: Barbara
authors: B
authors: Knollmann-Ritschel
authors: Department of Pathology, Uniformed Services University of the Health Sciences (USUHS), School of Medicine, Bethesda, Maryland, United States of America.
authors: Michael J
authors: MJ
authors: Daly
authors: Radiation Combined Injury Program, Armed Forces Radiobiology Research Institute (AFRRI), Bethesda, Maryland, United States of America.
authors: Juliann G
authors: JG
authors: Kiang
authors: Department of Pathology, Uniformed Services University of the Health Sciences (USUHS), School of Medicine, Bethesda, Maryland, United States of America.
authors: Radha K
authors: RK
authors: Maheshwari
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D000975:Antioxidants / Q000737:chemistry; D001853:Bone Marrow / Q000187:drug effects / Q000528:radiation effects; D016207:Cytokines / Q000097:blood; D011088:DNA Ligases / Q000378:metabolism; D034301:Deinococcus / Q000737:chemistry*; D015195:Drug Design; D005260:Female; D006801:Humans; D019169:Jurkat Cells / Q000187:drug effects / Q000528:radiation effects; D007970:Leukopenia / Q000188:drug therapy; D008345:Manganese / Q000737:chemistry; D008815:Mice, Inbred Strains; D010455:Peptides / Q000737:chemistry; D011832:Radiation Injuries / Q000517:prevention & control; D011839:Radiation, Ionizing; D011837:Radiation-Protective Agents / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology*; D013163:Splenomegaly / Q000188:drug therapy
chemical_list: D018952:Antigens, CD34; D000975:Antioxidants; D016207:Cytokines; D010455:Peptides; D011837:Radiation-Protective Agents; D008345:Manganese; D011088:DNA Ligases