|Proteasome inhibitors MG132 and lactacystin regulate the radiation-induced protein synthesis in human lymphocytes|
- Ivanova, V. Nikolov, R. Georgieva, I. Rupova, R. Boteva
De novo protein synthesis is an important cellularprocess carried out on numerous cytosolic ribosome complexes regulated by the proteasome system which supplies the amino acids necessary for the translation processes. It has been shown that ionizing gamma radiation induces changes in gene expression on translation rather than transcription level, stimulates de novo protein synthesis and this protects cells exposed to radiation-induced genotoxic stress. In this study, we analyzed the changes in the level of newly synthesized proteins in lymphocytes treated with the proteasome inhibitors MG132 and lactacystin, and exposed to radiation doses ranging from 0.5 to 8 Gy as an important part of the early cellular radiation response. Changes in the levels of newly synthesized proteins induced upon treatment with four different concentrations of MG132 or lactacystin and/or radiation exposure were studied by incorporation of L-Methionine-1-14C and measured on liquid scintilator. The results showed that the inhibitors exerted concentration-dependent effects on de novo protein synthesis in lymphocytes and in combination with γ-radiation stimulated in dose-dependent manner de novo protein synthesis in lymphocytes as a part of the early radiation response of normal human lymphocytes. It has been concluded that the reversible MG132 and irreversible proteasome inhibitor lactacystin can effectively modify the radiation response and exert protection on lymphocytes exposed to γ-IR.
|Key words PROTEIN SYNTHESIS. GAMMA RADIATION .