[TNF-induced apoptosis and necrosis in myeloleukemia cells HL-60 is regulated by reactive oxygen metabolites depending on a cell cycle phase]. / TNF-indutsiruemyi apoptoz i nekroz v kletkakh mieloleikoza HL-60 reguliruetsia reaktivnymi metabolitami kisloroda v zavisimosti ot fazy kletochnogo tsikla.

UNLABELLED: TNF is the known death receptor ligand which induce apoptosis and necrosis. Reactive oxygen metabolites, ceramide (synthesized de novo and as a product of sphingomyelin cycle), and caspases have been implicated as potential mediators of cell death. Their mechanistic relationship remains to be elucidated. The presence and activation of executor caspase-3 has been found to be regulated during both TNF-induced apoptosis and necrosis on their early stages. TNF-induced cell damage, suggesting the induction of both, apoptosis and necrosis, depended on the cell cycle. Necrosis induced by TNF was inhibited by denitrophenol (DNP). Pretreatment of these cells with exogenous bacterial sphingomyelinase (SMase) potentiates TNF-alpha induced apoptosis only, suggesting the role of ceramide from sphingomyelin cycle in TNF signaling pathways of apoptosis. DNP was found to initiate necrosis after SMase and TNF common action. The role of ceramide synthesis in enhanced ceramide generation in response to oxidant stress was shown using inhibitor of ceramide synthase--fumonisin B1. Its effect was found to be modulated by mitochondrial chain respiration inhibitors. Monoclonal antibodies to TNF-alpha receptors R1 and R2 exhibit the more high level of necrosis compared with TNF and both regulated by DNP and phospholipase A2. TNF-R2 effect was not found previously. CONCLUSION: Ceramide synthesis and sphingomyelin breakdown, caspase activation and reactive oxygen metabolites production are required for the TNF-alpha-induced apoptosis and necrosis which may be regulated dependently on cell cycle. TNF-initiated necrosis seems to be the disrupted apoptotic program and may be classified as aponecrosis.

[The role of adhesion molecules (ICAM-1 and E-selectin) in development of diabetic microangiopathies]. / Rol' molekul adgezii (ICAM-1 i E-selektin) v razvitii diabeticheskikh mikroangiopatii.

AIM: To examine the expression of the intercellular adhesion molecule-1 (ICAM-1, CD54) on the surface of leukocytes and a soluble E-selectin (CD62) level in patients with diabetes mellitus type 1 (DM1) at various stages of diabetic nephropathy and retinopathy. MATERIAL AND METHODS: 42 patients with newly diagnosed and long-standing DM1 with presence or absence of microangiopathy (diabetic nephropathy and retinopathy) were examined. Routine laboratory, ophthalmologic tests, a special immunological test with ICAM-1 expression and soluble E-selectin (sES) examination were performed. RESULTS: The tests show increased ICAM-1 expression and sES level in all the patients vs controls. In newly diagnosed DM1 a high sES level was observed. In long-standing DM1 and absence of microangiopathy a sES level was also high. In patients with neovascularisation and proteinuria the sES level was two times higher than that in other subgroups. We also found an increased percentage of ICAM-1, CD54-positive lymphocytes and granulocytes in patients with microalbuminuria and especially with proteinuria and neovascularization. There were no correlations of ICAM-1 and sES levels with sex, DM duration, cholesterol and triglycerides. CONCLUSION: The findings show endothelium and leukocytes activation at early disease stages. Enhanced endothelium and leukocytes activation is associated with late complications.