期刊
BIOCHEMISTRY-MOSCOW
卷 75, 期 6, 页码 702-707出版社
MAIK NAUKA/INTERPERIODICA/SPRINGER
DOI: 10.1134/S0006297910060040
关键词
heat shock protein 90; geldanamycin; toxic stress; lipopolysaccharide; NF-kappa B and SAPK/JNK signal pathways; cytokines; nitric oxide; Tlr-4
资金
- Russian Foundation for Support of Leading Scientific Schools [NSh-3202.2010.4]
- Russian Foundation [10-04-00351]
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-alpha, IFN-gamma, 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-kappa B 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-kappa B and SAPK/JNK. The results suggest Hsp90 might be a therapeutic target in diseases accompanied by acute toxic stress.
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