Modulating Radiation Resistance: Novel Protection Paradigms Based on Defenses against Ionizing Radiation in the Extremophile Deinococcus radiodurans
Abstract
For Deinococcus radiodurans and other bacteria which are extremely resistant to ionizing radiation (IR) and desiccation, a mechanistic link exists between resistance, manganese accumulation, and protein protection. We have demonstrated that ultrafiltered, protein-free preparations of D. radiodurans cell extracts prevent protein oxidation at massive doses of IR. In comparison, ultrafiltrates from IR-sensitive bacteria were not protective. The D. radiodurans ultrafiltrate was enriched in Mn, phosphate, nucleosides, and bases and peptides. When combined in vitro at concentrations approximating those in D. radiodurans, these constituents interacted highly synergistically and formed complexes which preserved the activity of large, multimeric enzymes exposed to 50,000 Gy, conditions which obliterated DNA. When applied in vivo, they protected Escherichia coli and human cells from extreme cellular insults caused by IR. By establishing how proteins can be protected against indirect damage caused by gamma-rays delivered in vast doses, our findings provide the basis for a new approach to radioprotection.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 10, 2010
- Accession Number
- ADA523366
Entities
People
- Michael J. Daly
Organizations
- Uniformed Services University of the Health Sciences