Compositions containing nucleosides and manganese and their uses
This invention encompasses methods of preserving protein function by contacting a protein with a composition comprising one or more purine or pyrimidine nucleosides (such as e.g., adenosine or uridine) and an antioxidant (such as e.g., manganese). In addition, the invention encompasses methods of treating and/or preventing a side effect of radiation exposure and methods of preventing a side effect of radiotherapy comprising administration of a pharmaceutically effective amount of a composition comprising one or more purine or pyrimidine nucleosides (such as e.g., adenosine or uridine) and an antioxidant (such as e.g., manganese) to a subject in need thereof. The compositions may comprise D. radiodurans extracts.
1. A method of protecting mammalian cells from ionizing radiation-induced damage, the method comprising administering a protective amount of a protein-free D. radiodurans ultrafiltrate to the mammalian cells, wherein the ultrafiltrate does not contain molecules having a molecular weight of greater than 3 kDa.
2. The method of claim 1 , wherein the ionizing radiation is selected from the group consisting of UV light, alpha radiation, beta radiation, gamma radiation, X-ray radiation and neutron radiation.
3. The method of claim 1 , wherein the protein-free D. radiodurans ultrafiltrate comprises one or more nucleosides selected from the group consisting of adenosine, uridine, β-pseudouridine, inosine, and mixtures thereof.
4. The method of claim 1 , wherein the protein-free D. radiodurans ultrafiltrate comprises one or more antioxidants selected from the group consisting of manganese, MnCl 2 and manganous phosphate.
5. The method of claim 1 , wherein the protein-free D. radiodurans ultrafiltrate comprises an amino acid selected from the group consisting of alanine, valine, and leucine.
6. The method of claim 3 , wherein the concentration of the one or more nucleosides comprises about 1 to about 15 mM of adenosine and/or uridine.
7. The method of claim 4 , wherein concentration of the one or more antioxidants comprises about 1 to about 12.5 mM of manganese.
8. The method of claim 1 , wherein the protein-free D. radiodurans ultrafiltrate produced by a method comprising the steps of:
harvesting a D. radiodurans culture by centrifugation;
lysing the D. radiodurans culture to create a D. radiodurans lysate;
centrifuging the D. radiodurans lysate for a time and under conditions sufficient to create a supernatant;
passing the supernatant through a less than 3 kiloDalton filter; and
boiling the supernatant for about 15 to about 45 minutes, to produce the protein-free D. radiodurans extract
wherein the protein-free D. radiodurans ultrafiltrate is resistant to boiling, and cell-free.
9. The method of claim 1 , wherein the protein-free D. radiodurans ultrafiltrate is administered to the mammalian cells prior to exposure of the mammalian cells to the ionizing radiation.
10. The method of claim 1 , wherein the ionizing radiation-induced damage is selected from the group consisting of cell apoptosis, protein carbonylation within the cells and protein oxidation within the cells.