[Effect of geldanamycin on the expression of signal proteins and heat shock proteins in normal mice lymphocytes].
The effects of geldanamycin, which is known as inhibitor of heat shock protein 90 activities, on expression of several signal and 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 geldanamycin resulted in decrease in transcription factor NF-kappaB amount, as well as decrease in its phosphorylated form, pNF-kappaB, and lowering in its suppressor, IkappaB-alpha. Besides, cells cultivated with geldanamycin demonstrated significant decrease in the amount of protein kinase SAPK(JNK). The modifications in signal pathways, which had been induced by geldanamycin, pointed to direct influence of the antibiotics on cellular stress response to damaging impact. This assumption was examined with the model of cellular stress response induced by low-level laser radiation. It was proved that Hsp90-binding drug, geldanamycin, significantly decreased in vitro stress response to laser light via lowering the production of heat shock proteins, Hsp70 and Hsp25, both in irradiated lymphocytes and in theirs intracellular structures. These findings show the prospect for using of geldanamycin in various therapies that are compromised with objectionable side effects manifested as heightened stress response in immune cells.
Novoselova
T V
TV
Cherenkov
D A
DA
Khrenov
M O
MO
Glushkova
O V
OV
Lunin
S M
SM
Novoselova
E G
EG
Fesenko
E E
EE
D000818:Animals; D016227:Benzoquinones / Q000494:pharmacology*; D002478:Cells, Cultured; D015536:Down-Regulation; D015870:Gene Expression; D018840:HSP70 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D006360:Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D020672:I-kappa B Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D047029:Lactams, Macrocyclic / Q000494:pharmacology*; D007834:Lasers; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D008297:Male; D051379:Mice; D018832:Molecular Chaperones; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D013154:Spleen
D016227:Benzoquinones; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C486113:Hsbp1 protein, mouse; D020672:I-kappa B Proteins; D047029:Lactams, Macrocyclic; D018832:Molecular Chaperones; D016328:NF-kappa B; D009363:Neoplasm Proteins; C000606205:Nfkbia protein, mouse; D047428:Protein Kinase Inhibitors; D000072000:NF-KappaB Inhibitor alpha; D048670:MAP Kinase Kinase 4; C001277:geldanamycin