RESUMO
The mechanisms of VEGF-mediated effects on endothelial cells during cancer development and progression is not clear. In present study the biological effects of VEGF, VEGF-rich culture medium of peritoneal macrophages from mice with Lewis lung carcinoma were studied on MAEC cell line under conditions of unfed culture. We have shown that VEGF increased cell proliferation by the 5th day of culturing vs control and anti-VEGF-treated cells. This effect was associated with increased consumption of glucose and NO production by the 2nd day while decreased on the 5th day of cell culturing. VEGF-mediated NO production was dependent on Ca2+ ions. Block of Ca2+-channels (LaCl3) had more pronounced inhibitory effect vs chelator of Ca2+ ions (EDTA). It was shown that peritoneal macrophages are the main suppliers of VEGF at tumor angiogenesis, as evidenced by the data obtained on model system of endothelial cells synchronized in G0/G1 phase.
Assuntos
Cálcio/metabolismo , Carcinoma Pulmonar de Lewis/metabolismo , Células Endoteliais/efeitos dos fármacos , Macrófagos Peritoneais/metabolismo , Neovascularização Patológica/metabolismo , Fator A de Crescimento do Endotélio Vascular/farmacologia , Animais , Anticorpos Monoclonais/farmacologia , Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio/metabolismo , Carcinoma Pulmonar de Lewis/patologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Transformada , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Técnicas de Cocultura , Meios de Cultivo Condicionados/química , Meios de Cultivo Condicionados/farmacologia , Ácido Edético/farmacologia , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Feminino , Glucose/metabolismo , Lantânio/farmacologia , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/patologia , Camundongos , Neovascularização Patológica/patologia , Óxido Nítrico/biossíntese , Cultura Primária de Células , Fator A de Crescimento do Endotélio Vascular/biossínteseRESUMO
The work is dedicated to the research of the content of lipids and products of their peroxidation in rats thymocytes in experimental ulceration. It was found significant increase of the content of lipid peroxidation products diene conjugates (DC), malondialdehyde (MDA), schiff base (SB) in experimental models of gastric ulcers (ethanol and stress). It was established that under ethanol gastric the contents of DC increases by 1.8 times, MDA by 2.1 and SB by 1.3 times relative to control values. Under stress model it was observed an increase in the number of DC by 2 times, MDA by 1.9 and SB by 1.3 times relative to control. When ethanol and stress ulcers cholesterol increased by 1.7 and 1.5 times, triacylglycerol by 2 and 2.3 times and fatty acids by 2.2 and 1.9 times, respectively, relative to controls. Phosphatidylethanolamine content decreases by 1.5 and 1.3 times compared to control. Also, the stress model, it was observed reduction of phosphatidylinositol by 1.3 times and increased lizofosfatydylholinu by 1.7 times compared to control. Therefore, our studies indicate quantitative changes of lipid content (neutral- and phospholipids) in rats' thymocytes under experimental (ethanol and stress) ulceration. The reason of this changes may be activation of lipid peroxidation, as shown by the increase of lipid peroxidation products' (DK, MDA, SB) content.
Assuntos
Metabolismo dos Lipídeos , Peroxidação de Lipídeos , Úlcera Gástrica/metabolismo , Timócitos/metabolismo , Animais , Modelos Animais de Doenças , Feminino , Metabolismo dos Lipídeos/imunologia , Peroxidação de Lipídeos/imunologia , Peróxidos Lipídicos/metabolismo , Masculino , Ratos , Úlcera Gástrica/etiologia , Úlcera Gástrica/imunologia , Timócitos/imunologiaRESUMO
Features of free radical processes and their impact on the implementation of immunocompetent cells of their functions under conditions of peptic ulcer are insufficiently studied today. Reduced activity of catalase 1.7 and 3.4 times and that of glutathione peroxidise ~ 2.0 times, accordingly, were observed in both models of gastric ulceration (stress ulcer and ethanol one). Enzymatic activity of superoxide dismutase decreased 1.5 times and activity of glutathione transferase increased 1.8 times in the stress model in contrast to the ethanol model of stomach ulcer. Obtained results indicate the exhaustion of antioxidant system in rats' thymocytes under experi- mental ulcerogenesis. These data confirm complex negative effect of ulcer on the organism.
