Role of heat shock protein Hsp90 in formation of protective reactions in acute toxic stress

The involvement of heat shock protein Hsp90 in pro-inflammatory response in male NMRI mice under conditions of acute toxic stress, caused by lipopolysaccharide from Gram negative bacteria, was studied using geldanamycin, a specific blocker of the activity of this protein. It is shown that the introd...

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Bibliographic Details
Published in:Biochemistry (Moscow) 2010-06, Vol.75 (6), p.702-707
Main Authors: Glushkova, O. V., Novoselova, T. V., Khrenov, M. O., Parfenyuk, S. B., Lunin, S. M., Fesenko, E. E., Novoselova, E. G.
Format: Article
Language:English
Subjects:
Animals
Antibiotics
Antibiotics, Antineoplastic - pharmacology
Benzoquinones - pharmacology
Biochemistry
Biological products
Biomedical and Life Sciences
Biomedicine
Bioorganic Chemistry
Heat shock proteins
HSP90 Heat-Shock Proteins - antagonists & inhibitors
HSP90 Heat-Shock Proteins - metabolism
HSP90 Heat-Shock Proteins - physiology
Interferon
Interferon-gamma - blood
Interleukin-1 - blood
Interleukin-10 - blood
Lactams, Macrocyclic - pharmacology
Life Sciences
Lipopolysaccharides - toxicity
Macrophages - drug effects
Macrophages - immunology
Macrophages - metabolism
Male
Mice
Microbiology
Mitogens
NF-kappa B - metabolism
Nitric oxide
Nitric Oxide - metabolism
Rodents
Signal Transduction
Toll-Like Receptor 4 - metabolism
Toxicity Tests, Acute
Toxicology
Tumor necrosis factor
Tumor Necrosis Factor-alpha - blood
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Summary:The involvement of heat shock protein Hsp90 in pro-inflammatory response in male NMRI mice under conditions of acute toxic stress, caused by lipopolysaccharide from Gram negative bacteria, was studied using geldanamycin, a specific blocker of the activity of this protein. It is shown that the introduction of geldanamycin lowers total intoxication of the organism upon acute toxic stress caused by endotoxin. Thus, a decrease in cytokine TNF-α, IFN-γ, IL-1, and IL-10 concentrations in blood serum of the geldanamycin-treated animals with acute toxic stress was found along with normalization of functional activity of nitric oxide producing peritoneal macrophages. Studying expression of receptor protein Tlr-4 as well of proteins of two signal cascades, NF-κB and SAPK/JNK, has shown that mechanisms of the geldanamycin protective effect are realized at the level of inhibition of Tlr-4 receptor expression, which provides for endotoxin-to-cell binding, and due to lowering the endotoxin-stimulated activation of signal cascades NF-κB and SAPK/JNK. The results suggest Hsp90 might be a therapeutic target in diseases accompanied by acute toxic stress.
ISSN:0006-2979
1608-3040
DOI:10.1134/S0006297910060040