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. 2022 Oct;506(1):202-205.
doi: 10.1134/S160767292205012X. Epub 2022 Oct 27.

Geldanamycin Enhances the Radioprotective Effect of Peroxyredoxin 6 in Irradiated 3T3 Fibroblasts

E G Novoselova  1 , O V Glushkova  2 , M G Sharapov  2 , M O Khrenov  2 , S B Parfenyuk  2 , S M Lunin  2 , T V Novoselova  2 , A K Mubarakshina  2 , R G Goncharov  2 , E E Fesenko  2
Affiliations

Geldanamycin Enhances the Radioprotective Effect of Peroxyredoxin 6 in Irradiated 3T3 Fibroblasts

E G Novoselova et al. Dokl Biochem Biophys. 2022 Oct.

Abstract

The aim of the study was to evaluate the possibility of increasing the radioprotective potential of peroxiredoxin 6 (Prdx6) and its mutant form S32A by their combined use with geldanamycin (GA) for 3T3 fibroblasts irradiated with X-rays at a dose of 6 Gy. The mutant enzyme S32A, which does not have phospholipase activity, exhibits a more pronounced radioprotective activity when combined with GA. The use of this combination of radioprotective drugs completely abolishes the peak of NF-κB activity in irradiated 3T3 cells. Another transcription factor, p53, which is an indicator of the level of cell apoptosis and increases upon irradiation, is also reduced by S32A in combination with GA. The low-molecular-weight protein p21, which is a marker of cell senescence and whose production increases upon irradiation, is also normalized when S32A is used in combination with GA. In addition, the use of this combination of radioprotective drugs significantly reduces the stress response of 3T3 cells to X-ray irradiation.

Keywords: 3T3 fibroblasts; X-ray radiation; apoptosis; cellular stress; senescence, peroxiredoxin 6, geldanamycin.

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