[Effect of ladasten on proliferative activity and apoptosis in peripheral blood T-lymphocytes ].
The effects of ladasten (0.1-10 microM) on the proliferative activity, apoptosis, and expression of the apoptosis protein regulators (bcl-2 and p53) was studied in 72-h cultures of T-lymphocytes of human peripheral blood activated by anti-CD3MCA. In the concentration interval from 0.01 to 1 microM, ladasten produced a comitogenic effect. The drug changed neither the activity of caspase 3 and the proportion of cells in the late apoptosis stage (Hoechst 33342 stain test), nor the bcl-2 expression, but increased the p53 expression in the activated cells. Irrespective of the concentration, ladasten protected activated lymphocytes in the cell culture from apoptosis induced by the topoisomerase I inhibitor camptothecin or by hydrogen peroxide (provided that the drug was added to the culture simultaneously with the apoptosis inductor). At the same time, lymphocytes cultivated in the presence of ladasten acquired resistance with respect to apoptosis induced by hydrogen peroxide, but not by camptothecin. It is suggested that the immunomodulant activity of ladasten are related to the comitogenic effect and the increase in resistance of the activated T-lymphocytes with respect to non-receptor-induced apoptosis.
Vakhitova
Iu V
IuV
Institute of Biochemistry and Genetics, Ufa Scientific Center, Russian Academy of Sciences, Ufa, Bashkortostan, 450054 Russia.
Sibiriak
S V
SV
Kurchatova
N N
NN
Seredenin
S B
SB
D000218:Adamantane / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D017209:Apoptosis / Q000187:drug effects*; D017252:CD3 Complex / Q000276:immunology; D002166:Camptothecin / Q000494:pharmacology; D002478:Cells, Cultured; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008934:Mitogens / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D059004:Topoisomerase I Inhibitors; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D008934:Mitogens; D019253:Proto-Oncogene Proteins c-bcl-2; D059004:Topoisomerase I Inhibitors; D016159:Tumor Suppressor Protein p53; D006861:Hydrogen Peroxide; D000218:Adamantane; D002166:Camptothecin