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Production of Heat Shock Proteins, Cytokines, and Nitric Oxide in Toxic Stress


E. G. Novoselova1*, O. V. Glushkova1, D. A. Cherenkov1, S. B. Parfenyuk1, T. V. Novoselova1, S. M. Lunin1, M. O. Khrenov1, I. V. Guzhova2, B. A. Margulis2, and E. E. Fesenko1

1Institute of Cell Biophysics, Russian Academy of Sciences, Institutskaya ul. 3, 142290 Pushchino, Moscow Region, Russia; fax: (0967) 33-0509; E-mail: elenanov@icb.psn.ru

2Institute of Cytology, Russian Academy of Sciences, Tikhoretskii pr. 3, 194064 St. Petersburg, Russia; fax: (812) 247-0341; E-mail: margulis@mail.cytspb.rssi.ru

* To whom correspondence should be addressed.

Received June 30, 2005; Revision received September 29, 2005
Expression of heat shock proteins Hsp27, Hsp90, and Hsp70 and production of tumor necrosis factors (TNF-alpha, TNF-beta), interferon-gamma (IFN-gamma), interleukin-2, -3, -6, and nitric oxide (NO) were studied under conditions of acute and chronic intoxication of animals with lipopolysaccharides. Injection of endotoxin increased expression of heat shock proteins Hsp70 and Hsp90-alpha in mouse cells. Acute toxic stress also provoked a sharp increase in the production of TNF-alpha, TNF-beta, and NO in mouse cells. The production of other cytokines (interleukins and IFN-gamma) was changed insignificantly. In the model of chronic toxic stress, changes in the production of Hsp70, Hsp90, TNF, and NO were followed during 11 days after the beginning of the toxin injections. The expression of Hsp70 and Hsp90 in acute stress was significantly higher than at the final stage of the chronic exposure. The changes in the TNF and NO productions, on one hand, and the production of heat shock proteins, on the other hand, were synchronous. The findings indicate that repeated injections of increasing endotoxin doses result in a decreased ability of the body cells to respond to stress by overproduction of heat shock proteins, TNF, and NO.
KEY WORDS: toxic stress, heat shock protein production, tumor necrosis factor, interferon-gamma, interleukins, nitric oxide

DOI: 10.1134/S0006297906040055