RESUMEN
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.
Asunto(s)
Fosfatidilinositol 3-Quinasa Clase Ia/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Neutrófilos/metabolismo , Lectinas de Plantas/farmacología , Receptores Mitogénicos/química , Androstadienos/farmacología , Estudios de Casos y Controles , Agregación Celular/efectos de los fármacos , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Células Cultivadas , Citosol/efectos de los fármacos , Citosol/metabolismo , Diabetes Mellitus Tipo 1/patología , Humanos , Activación Neutrófila/efectos de los fármacos , Neutrófilos/efectos de los fármacos , Neutrófilos/patología , Inhibidores de Proteínas Quinasas/farmacología , Transporte de Proteínas/efectos de los fármacos , Receptores Mitogénicos/metabolismo , Transducción de Señal/efectos de los fármacos , WortmaninaRESUMEN
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.
Asunto(s)
Membrana Celular/metabolismo , Diabetes Mellitus Tipo 1/enzimología , Leucocitos/enzimología , Fosfatidilinositol 3-Quinasa/metabolismo , Subunidades de Proteína/metabolismo , Receptores de Superficie Celular/metabolismo , Transducción de Señal/efectos de los fármacos , Adulto , Androstadienos/farmacología , Western Blotting , Fraccionamiento Celular , Membrana Celular/efectos de los fármacos , Citosol/metabolismo , Diabetes Mellitus Tipo 1/patología , Electroforesis en Gel de Poliacrilamida , Activación Enzimática/efectos de los fármacos , Glicoproteínas/metabolismo , Humanos , Insulina/metabolismo , Lectinas/farmacología , Leucocitos/efectos de los fármacos , Leucocitos/patología , Inhibidores de las Quinasa Fosfoinosítidos-3 , Inhibidores de Proteínas Quinasas/farmacología , Subunidades de Proteína/antagonistas & inhibidores , Ácidos Siálicos/química , Ácidos Siálicos/metabolismo , WortmaninaRESUMEN
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.