• Publikační typ
• abstrakt z konference MeSH

• MeSH
• biologické markery analýza   MeSH
• buněčné dělení účinky léků   MeSH
• cévní endotel cytologie   sekrece   MeSH
• erythropoetin farmakologie   MeSH
• faktor stimulující kolonie granulocytů farmakologie   MeSH
• inhibitor aktivátoru plazminogenu 1 sekrece   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH

• MeSH
• adjuvancia imunologická MeSH
• HIV-1 MeSH
• interferon gama MeSH
• preklinické hodnocení léčiv MeSH
• replikace viru MeSH
• tumor nekrotizující faktory MeSH

• MeSH
• arterioskleróza etiologie   imunologie   MeSH
• cévní buněčněadhezivní molekula-1 imunologie   MeSH
• cévní endotel účinky léků   MeSH
• finanční podpora výzkumu jako téma MeSH
• hyperglykemie imunologie   MeSH
• mezibuněčná adhezivní molekula-1 imunologie   MeSH
• molekuly buněčné adheze imunologie   MeSH
• techniky in vitro MeSH
• venae umbilicales MeSH

The endothelial barrier function is tightly controlled by a broad range of signaling cascades including nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway. It has been proposed that disturbances in NO and cGMP production could interfere with proper endothelial barrier function. In this study, we assessed the effect of interferon-gamma (IFN-gamma), a pro-inflammatory cytokine, on NO and cGMP levels and examined the mechanisms by which NO and cGMP regulate the IFN-gamma-mediated HUVECs hyperpermeability. The flux of fluorescein isothiocyanate-labeled dextran across cell monolayers was used to study the permeability of endothelial cells. Here, we found that IFN-gamma significantly attenuated basal NO concentration and the increased NO levels supplied by a NO donor, sodium nitroprusside (SNP). Besides, application of IFN-gamma also significantly attenuated both the basal cGMP concentration and the increased cGMP production donated by a cell permeable cGMP analogue, 8-bromo-cyclic GMP (8-Br-cGMP). In addition, exposure of the cell monolayer to IFN-gamma significantly increased HUVECs basal permeability. However, L-NAME pretreatment did not suppress IFN-gamma-induced HUVECs hyperpermeability. L-NAME pretreatment followed by SNP or SNP pretreatment partially reduced IFN-gamma-induced HUVECs hyperpermeability. Pretreatment with a guanylate cyclase inhibitor, 6-anilino-5,8-quinolinedione (LY83583), led to a further increase in IFN-gamma-induced HUVECs hyperpermeability. The findings suggest that the mechanism underlying IFN-gamma-induced increased HUVECs permeability is partly related to the inhibition of NO production.

• MeSH
• donory oxidu dusnatého farmakologie   MeSH
• endoteliální buňky pupečníkové žíly (lidské) účinky léků   metabolismus   MeSH
• guanosinmonofosfát cyklický analogy a deriváty   metabolismus   farmakologie   MeSH
• guanylátcyklasa antagonisté a inhibitory   MeSH
• inhibitory enzymů farmakologie   MeSH
• interferon gama farmakologie   MeSH
• kapilární permeabilita účinky léků   MeSH
• lidé MeSH
• NG-nitroargininmethylester farmakologie   MeSH
• nitroprusid farmakologie   MeSH
• oxid dusnatý metabolismus   MeSH
• permeabilita buněčné membrány MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

The effects in vitro of 2,3-dehydrosilybin and several galloyl esters and methyl ethers on the viability, proliferation, and migration of human umbilical vein endothelial cells (HUVECs) were evaluated. The monogalloyl esters were synthesized by a chemoselective esterification method or by Steglich esterification of suitably protected 2,3-dehydrosilybin (1) with protected gallic acid. 2,3-Dehydrosilybin (1) displayed more potent cytotoxic, antiproliferative, and antimigratory activities (IC50 12.0, 5.4, and 12.2 μM, respectively) than silybin. The methylated derivatives were less active, with the least potent being 3,7-di-O-methyl-2,3-dehydrosilybin (6). On the other hand, galloylation at C-7 OH and C-23 OH markedly increased the cytotoxicity and the effects on the proliferation and migration of HUVECs. The most active derivative was 7-O-galloyl-2,3-dehydrosilybin (13; IC50 value of 3.4, 1.6, and 4.7 μM in the cytotoxicity, inhibition of proliferation, and antimigratory assays, respectively). Overall, this preliminary structure-activity relationship study demonstrated the importance of a 2,3-double bond, a C-7 OH group, and a galloyl moiety in enhancing the activity of flavonolignans toward HUVECs.

• MeSH
• endoteliální buňky pupečníkové žíly (lidské) účinky léků   MeSH
• kyselina gallová farmakologie   MeSH
• lidé MeSH
• methylethery farmakologie   MeSH
• molekulární struktura MeSH
• scavengery volných radikálů chemie   MeSH
• silymarin chemie   farmakologie   MeSH
• viabilita buněk účinky léků   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Antiangiogenic activity of the brassinosteroid plant hormones (BRs) and their derivative cholestanon was investigated in human umbilical vein endothelial cells (HUVEC) and in human microvascular endothelial cells (HMEC-1). 24-Epibrassinolide and 28-homocastasterone from group of 21 tested natural BRs inhibited migration of HUVEC cells. Seven tested BRs decreased the number of tubes significantly. Synthetic analogue cholestanon inhibited angiogenesis in vitro more effectively than natural BRs. Because of the similarity of BRs to human steroids, we have also studied interactions of BRs with human steroid receptors. Synthetic BRs cholestanon showed agonistic effects on estrogen-receptor-α, estrogen-receptor-β and androgen receptor. Of the natural BRs, 24-epibrassinolide was found to be a weak antagonist of estrogen-receptor-α (ERα). Our results provide the first evidence that large group of BRs can inhibit in vitro angiogenesis of primary endothelial cells. BRs constitute a novel group of human steroid receptor activators or inhibitors with capacity to inhibit angiogenesis.

• MeSH
• alfa receptor estrogenů metabolismus   MeSH
• beta receptor estrogenů metabolismus   MeSH
• brassinosteroidy metabolismus   farmakologie   MeSH
• endoteliální buňky pupečníkové žíly (lidské) účinky léků   metabolismus   MeSH
• fyziologická neovaskularizace účinky léků   MeSH
• inhibitory angiogeneze metabolismus   farmakologie   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND/AIM: Stromal cells in the tumor microenvironment are primarily considered as sources of promalignant factors. The objective of our study was to define the effect of extracellular matrix (ECM) produced by normal dermal or cancer-associated fibroblasts exposed to adhesion/growth-regulatory lectin galectin-1 on human umbilical vein endothelial cells (HUVECs). MATERIALS AND METHODS: Fibroblasts were cultured for 10 days with lectin, followed by removing cellular constituents after an osmotic shock. Freshly-isolated HUVECs were placed on the ECM. In parallel, HUVECs were seeded on untreated and gelatin-coated surfaces as controls. A positive control for growth of HUVECs culture using medium supplemented with vascular endothelial growth factor completed the test panel. Cells were kept in contact to the substratum for two days and then processed for immunocytochemistry. RESULTS: HUVECs seeded on fibroblast-generated ECM presented a comparatively high degree of proliferation. Furthermore, contact to substratum produced by tumor-associated fibroblasts led to generation of a meshwork especially rich in fibronectin. CONCLUSION: Galectin-1 is apparently capable to trigger ECM production favorable for growth of HUVECs, prompting further work on characterizing structural features of the ECM and in situ correlation of lectin presence, ECM constitution and neoangiogenesis.

• MeSH
• endoteliální buňky pupečníkové žíly (lidské) fyziologie   MeSH
• extracelulární matrix metabolismus   MeSH
• fibroblasty fyziologie   MeSH
• galektin 1 farmakologie   MeSH
• kultivované buňky MeSH
• lidé MeSH
• nádorové mikroprostředí * MeSH
• proliferace buněk účinky léků   MeSH
• vaskulární endoteliální růstový faktor A farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

UNLABELLED: Carbon nanotubes (CNTs) exhibit a number of unique properties that make them attractive for various nanomedicine applications including their intravascular use. Therefore, the vascular toxicity of CNTs is a critical safety concern and methods of CNTs toxicity modulation are of great interest. Here, we report that carboxylated multiwalled carbon nanotubes (MWCNTs) induce a decrease in viability of cultured human umbilical vein endothelial cells (HUVECs) associated with the profound accumulation of autophagosomes. This autophagosome accumulation was mTOR kinase independent and was caused by blockade of the autophagic flux rather than by activation of autophagy. Stimulation of the autophagic flux with 1nmol/L bafilomycin A1 attenuated the cytotoxicity of carboxylated MWCNTs in HUVECs and was associated with the extracellular release of the nanomaterial in autophagic microvesicles. Thus, pharmacological stimulation of the autophagic flux may represent a new method of cytoprotection against toxic effects of nanomaterials. FROM THE CLINICAL EDITOR: This study investigates the mechanisms of toxicity of multiwalled carbon nanutubes on human endothelial cells, concluding that pharmacological stimulation of autophagic flux may represent a new method of cytoprotection against the toxic effects of these nanomaterials.

• MeSH
• autofagie fyziologie   MeSH
• endoteliální buňky pupečníkové žíly (lidské) MeSH
• endoteliální buňky účinky léků   metabolismus   MeSH
• exocytóza účinky léků   MeSH
• lidé MeSH
• makrolidy farmakologie   MeSH
• nanostruktury toxicita   MeSH
• nanotrubičky uhlíkové * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Research Support, U.S. Gov't, P.H.S. MeSH

Besides its classical function as an orchestrator of calcium and phosphorus homeostasis, vitamin D also affects insulin secretion and tissue efficiency. A number of studies have consistently reported the inverse relationship between vitamin D deficiency and type 2 diabetes. Activation of certain metabolic pathways and down-stream transcription factors may protect from glucolipotoxicity and their targeted activation -e.g. by vitamin D - might explain the detrimental role of vitamin D deficiency in diabetes. The aim of the study was to quantify gene and protein expression of selected enzymes involved in the protection from glucolipotoxicity, specifically glyoxalase 1 (GLO1), and other enzymes with antioxidant activity - hemoxygenase (HMOX), thiamin pyrophosphokinase (TPK1) and transketolase (TKT), under normo- and hyperglycemic conditions and upon addition of vitamin D in peripheral blood mononuclear cells (PBMCs) and human umbilical vein endothelial cells (HUVEC). The results of our study indicate that the active form of vitamin D regulates gene expression of enzymes opposing the harmful effect of glucolipotoxicity whose activities appear to be suppressed by hyperglycemia. However, we were unable to confirm this effect on protein expression. While we cannot speculate on the effect of vitamin D on diabetes itself our results support its role in the protection against existing glucolipotoxicity therefore possibly translating into the prevention of development of diabetic complications.

• MeSH
• endoteliální buňky pupečníkové žíly (lidské) účinky léků   enzymologie   MeSH
• homeostáza účinky léků   MeSH
• inzulin sekrece   MeSH
• kultivované buňky MeSH
• laktoylglutathionlyasa genetika   metabolismus   MeSH
• leukocyty mononukleární účinky léků   enzymologie   MeSH
• lidé MeSH
• regulace genové exprese MeSH
• thiaminpyrofosfokinasa genetika   metabolismus   MeSH
• transketolasa genetika   metabolismus   MeSH
• vitamin D farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH