Small-molecule antioxidant proteome-shields in Deinococcus radiodurans.
For Deinococcus radiodurans and other bacteria which are extremely resistant to ionizing radiation, ultraviolet radiation, and desiccation, a mechanistic link exists between resistance, manganese accumulation, and protein protection. We show that ultrafiltered, protein-free preparations of D. radiodurans cell extracts prevent protein oxidation at massive doses of ionizing radiation. In contrast, ultrafiltrates from ionizing radiation-sensitive bacteria were not protective. The D. radiodurans ultrafiltrate was enriched in Mn, phosphate, nucleosides and bases, and peptides. When reconstituted in vitro at concentrations approximating those in the D. radiodurans cytosol, peptides interacted synergistically with Mn(2+) and orthophosphate, and preserved the activity of large, multimeric enzymes exposed to 50,000 Gy, conditions which obliterated DNA. When applied ex vivo, the D. radiodurans ultrafiltrate protected Escherichia coli cells and human Jurkat T cells from extreme cellular insults caused by ionizing radiation. By establishing that Mn(2+)-metabolite complexes of D. radiodurans specifically protect proteins against indirect damage caused by gamma-rays delivered in vast doses, our findings provide the basis for a new approach to radioprotection and insight into how surplus Mn budgets in cells combat reactive oxygen species.
Daly
Michael J
MJ
Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, United States of America. mdaly@usuhs.edu
Gaidamakova
Elena K
EK
Matrosova
Vera Y
VY
Kiang
Juliann G
JG
Fukumoto
Risaku
R
Lee
Duck-Yeon
DY
Wehr
Nancy B
NB
Viteri
Gabriela A
GA
Berlett
Barbara S
BS
Levine
Rodney L
RL
D000975:Antioxidants / Q000378:metabolism*; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects; D004260:DNA Repair; D034301:Deinococcus / Q000378:metabolism / Q000528:radiation effects*; D005720:Gamma Rays; D006801:Humans; D019169:Jurkat Cells; D020543:Proteome / Q000378:metabolism*; D011837:Radiation-Protective Agents / Q000378:metabolism*
D000975:Antioxidants; D020543:Proteome; D011837:Radiation-Protective Agents