ABSTRACT
It is shown that reduction of beta,D-galactosyl-containing carbohydrate determinants ofglycoconjugates on theplasmatic membrane of segmentonuclear neutrophills of peripheral blood under type 1 diabetes mellitus (DM) is correlated with changes in aggregation of these cells and may cause their functional disorder. Changes in the parameters of ricin-induced neutrophil activation after inhibition of the phosphatidylinositol-3'-kinase (PI-3'-kinase) enzyme with wortmannin indicated that the functional state ofpolymorphonuclear leukocytes is mediated by signaling pathways in which PI-3'-kinase is involved. Thus, PI-3'-kinase-dependent signal networks are involved in the processes of signal transduction through galactosyl-containing glycoprotein receptors into neutrophilic leukocytes. Inertness of the intensity formation in time ofneutrophil granulocyte cell response on RCA-induced translocation of the p85alpha regulatory subunit of PI-3'-kinase from the cytosolic to the membrane fraction under type 1 DM is a consequence of changes in the number or structure of plasmatic galactosyl-containing glycoprotein receptors. The revealed changes may be etiologic premise of diabetic complications and chronic diseases that impair the functional condition of patients with type 1 DM.
Subject(s)
Class Ia Phosphatidylinositol 3-Kinase/metabolism , Diabetes Mellitus, Type 1/metabolism , Neutrophils/metabolism , Plant Lectins/pharmacology , Receptors, Mitogen/chemistry , Androstadienes/pharmacology , Case-Control Studies , Cell Aggregation/drug effects , Cell Membrane/drug effects , Cell Membrane/metabolism , Cells, Cultured , Cytosol/drug effects , Cytosol/metabolism , Diabetes Mellitus, Type 1/pathology , Humans , Neutrophil Activation/drug effects , Neutrophils/drug effects , Neutrophils/pathology , Protein Kinase Inhibitors/pharmacology , Protein Transport/drug effects , Receptors, Mitogen/metabolism , Signal Transduction/drug effects , WortmanninABSTRACT
The influence of wortmannin and sialospecific lectins on the translocation of p85alpha regulatory subunit of phosphatidylinositol-3'-kinase (PI-3'-kinase) between membrane and cytosolic fractions of the mononuclear and polymorphonuclear leukocytes in healthy donors and patients with type 1 diabetes mellitus (DM) was investigated. It was found out that under type 1 DM PI-3'-kinase takes active part in the transduction of lectin-induced signal through membrane glycoprotein receptors that contain terminal sialic acids linked to subterminal carbohydrate residues with (alpha2-->6) glycosidic bond.
Subject(s)
Cell Membrane/metabolism , Diabetes Mellitus, Type 1/enzymology , Leukocytes/enzymology , Phosphatidylinositol 3-Kinase/metabolism , Protein Subunits/metabolism , Receptors, Cell Surface/metabolism , Signal Transduction/drug effects , Adult , Androstadienes/pharmacology , Blotting, Western , Cell Fractionation , Cell Membrane/drug effects , Cytosol/metabolism , Diabetes Mellitus, Type 1/pathology , Electrophoresis, Polyacrylamide Gel , Enzyme Activation/drug effects , Glycoproteins/metabolism , Humans , Insulin/metabolism , Lectins/pharmacology , Leukocytes/drug effects , Leukocytes/pathology , Phosphoinositide-3 Kinase Inhibitors , Protein Kinase Inhibitors/pharmacology , Protein Subunits/antagonists & inhibitors , Sialic Acids/chemistry , Sialic Acids/metabolism , WortmanninABSTRACT
NO-synthase activity, the content of stable products of NO metabolism (nitrites and nitrates) as well as fragmented DNA as biochemical marker of apoptosis have been determined in segmentonuclear neutrophilic granulocytes and mononuclear leukocytes in blood of healthy donors and patients with type 1 diabetes mellitus. It was found that activation of apoptosis in polymorphonuclear and mononuclear blood leukocytes under diabetes mellitus was accompanied by an elevation of NO-synthase activity and the content of stable NO metabolites. This suggests an increase of proapoptotic action of nitric oxide in immunocompetent blood cells under the pathology studied.
