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Effect of geldanamycin on expression of signal proteins and heat-shock proteins in normal mouse lymphocytes

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Abstract

Effects of geldanamycin (GA), a known inhibitor of the heat shock protein 90 (Hsp90) activity, on the expression of some signal proteins and various heat-shock proteins were studied by Western blot analysis in cultivated spleen lymphocytes isolated from male NMRI mice. It has been revealed that cultivating the cells with GA results in a significant decrease in the amount of transcription factor NF-κB, as well as in its phosphorylated form pNF-κB and the protein suppressing its activity, IκB-α. Furthermore, the presence of GA in the cell-cultivation medium produced a significant decrease in the amount of protein kinase SAPK/JNK. Such a GA-produced modification in the signal protein system suggests the participation of GA in the development of a stress response in an animal cell to damaging action. This suggestion was checked on a model of a cell’s stress response to the action of low-intensity laser radiation. It was proven that the Hsp90-binding agent, GA, significantly decreased in vitro the level of the stress response to laser radiation by decreasing the production of heatshock proteins, Hsp70 and Hsp25, both in irradiated isolated lymphocytes and in their intracellular structures. These findings open prospective uses for geldanamycin in various therapies that are accompanied by undesired side effects connected with increased levels of stress response in immune system cells.

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Abbreviations

Hsp:

heat-shock proteins

GA:

geldanamycin

TNF:

tumor necrosis factor

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Authors and Affiliations

  1. Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Moscow oblast, Russia

    T. V. Novoselova, D. A. Cherenkov, M. O. Khrenov, O. V. Glushkova, S. M. Lunin, E. G. Novoselova & E. E. Fesenko

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  1. T. V. Novoselova
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  2. D. A. Cherenkov
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  3. M. O. Khrenov
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  4. O. V. Glushkova
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  5. S. M. Lunin
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  6. E. G. Novoselova
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  7. E. E. Fesenko
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Correspondence to E. G. Novoselova.

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Original Russian Text © T.V. Novoselova, D.A. Cherenkov, M.O. Khrenov, O.V. Glushkova, S.M. Lunin, E.G. Novoselova, E.E. Fesenko, 2008, published in Tsitologiya, Vol. 50, No. 4, 2008.

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Novoselova, T.V., Cherenkov, D.A., Khrenov, M.O. et al. Effect of geldanamycin on expression of signal proteins and heat-shock proteins in normal mouse lymphocytes. Cell Tiss. Biol. 2, 366–372 (2008). https://doi.org/10.1134/S1990519X08040044

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  • DOI: https://doi.org/10.1134/S1990519X08040044

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