HSP90 Inhibitor Geldanamycin as a Radiation Response Modificator in Human Blood Cells.

Abstract

Heat shock protein 90 (Hsp90) is a highly conserved molecular chaperone, involved in the folding, assembly, stabilization and activation of numerous proteins with unrelated amino acid sequences and functions. Geldanamycin (GA), a natural benzoquinone, can inhibit the chaperone activity of Hsp90. It has been shown that GA can produce superoxide anions and increase the intracellular oxidative stress, which, in addition to the direct inhibition of Hsp90, might also contribute to the modifying effects of the inhibitor on the early response in human mononuclear cells exposed to ionizing radiation. The present study shows that GA antagonizes the radiation-induced suppression on MnSOD and catalase, key enzymes of the radical scavenging systems. By significantly up-regulating catalase levels over the entire range of doses from 0.5 to 4 Gy, the inhibitor of Hsp90 exerted adaptive protection and modified the early radiation response of the human blood cells.