Cytotoxicity of water-soluble fullerene in vascular endothelial cells

2006 ◽  
Vol 290 (6) ◽  
pp. C1495-C1502 ◽  
Author(s):  
Hideyuki Yamawaki ◽  
Naoharu Iwai
Keyword(s):  
Endothelial Cells ◽  
Cell Death ◽  
Vascular Endothelial Cells ◽  
Morphological Changes ◽  
Water Soluble ◽  
Specific Marker ◽  
Dependent Manner ◽  
Vascular Endothelial ◽  
Maximal Dose ◽  
Dose Dependent

Nanoscale materials are presently under development for diagnostic (nanomedicine) and electronic purposes. In contrast to the potential benefits of nanotechnology, the effects of nanomaterials on human health are poorly understood. Nanomaterials are known to translocate into the circulation and could thus directly affect vascular endothelial cells (ECs), causing vascular injury that might be responsible for the development of atherosclerosis. To explore the direct effects of nanomaterials on endothelial toxicity, human umbilical vein ECs were treated with 1–100 μg/ml hydroxyl fullerene [C60(OH)24; mean diameter, 7.1 ± 2.4 nm] for 24 h. C60(OH)24 induced cytotoxic morphological changes such as cytosolic vacuole formation and decreased cell density in a dose-dependent manner. Lactate dehydrogenase assay revealed that a maximal dose of C60(OH)24 (100 μg/ml) induced cytotoxic injury. Proliferation assay also showed that a maximal dose of C60(OH)24 inhibited EC growth. C60(OH)24 did not seem to induce apoptosis but caused the accumulation of polyubiquitinated proteins and facilitated autophagic cell death. Formation of autophagosomes was confirmed on the basis of Western blot analysis using a specific marker, light chain 3 antibody, and electron microscopy. Chronic treatment with low-dose C60(OH)24 (10 μg/ml for 8 days) inhibited cell attachment and delayed EC growth. In the present study, we have examined, for the first time, the toxicity of water-soluble fullerenes to ECs. Although fullerenes changed morphology in a dose-dependent manner, only maximal doses of fullerenes caused cytotoxic injury and/or death and inhibited cell growth. EC death seemed to be caused by activation of ubiquitin-autophagy cell death pathways. Although exposure to nanomaterials appears to represent a risk for cardiovascular disorders, further in vivo validations are necessary.

scholarly journals The Study on Angiotensin II Induced-Ferroptosis in Vascular Endothelial Cells

2021 ◽  
Author(s):  
hong fang ◽  
Chi liu ◽  
Omer Cavdar ◽  
Yi Shen
Keyword(s):  
Endothelial Cells ◽  
Angiotensin Ii ◽  
Molecular Marker ◽  
Analysis Of Variance ◽  
Vascular Endothelial Cells ◽  
Dependent Manner ◽  
Vascular Endothelial ◽  
Ang Ii ◽  
Valsartan Group ◽  
Dose Dependent

Abstract PurposeTo verify the effect of Angiotensin II on ferroptosis in vascular endothelial cells and clarify the related mechanism. MethodsHUVECs were evaluated for p53, P21,ALOX12, VEGF, MDA,GSH. Molecular marker impact upon AngII-induced ferroptosis was evaluated with students’ t-test，one-way analysis of variance (ANOVA).ResultsAs the concentration of Ang II increased，the level of ALOX12, P53,GSH and MDA increased in HUVECs. The expression of VEGFA in HUVECs is negatively correlated with dose of Ang II. Incubation of HUVECs in AngII and valsartan for 48hr reduces ALOX12, P21, GSH and MDA. Compared with the single AngII group, ALOX12, P21, GSH and MDA in valsartan group was decreased significantly（p=0.000）.In pifithrin-α hydrobromide-treated, ALOX12, P21, GSH and MDA was reduced significantly, as compared to valsartan group（p=0.000）. The most larger reduction in ALOX12, P21,GSH and MDA was pifithrin - α hydrobromide combined with valsartan group. In contrast, the expression of VEGFA increased significantly after HUVECs were treated with pifithrin - α hydrobromide and valsartan（p=0.000）.ConclusionsAngII can induce ferroptosis of vascular endothelial cells in a dose-dependent manner. The mechanism of AngII-induced ferroptosis may be regulated through the signal axis of ATR1,2-p53-ALOX12.

scholarly journals The Study on Angiotensin II Induced-ferroptosis in Vascular Endothelial Cells

2021 ◽  
Author(s):  
Hong Fang ◽  
Chi Liu ◽  
Omer Cavdar ◽  
Yi Shen
Keyword(s):  
Endothelial Cells ◽  
Angiotensin Ii ◽  
Molecular Marker ◽  
Analysis Of Variance ◽  
Vascular Endothelial Cells ◽  
Dependent Manner ◽  
Vascular Endothelial ◽  
Ang Ii ◽  
Valsartan Group ◽  
Dose Dependent

Abstract Background: To verify the effect of Angiotensin II on ferroptosis in vascular endothelial cells and clarify the related mechanism.Methods: HUVECs were evaluated for p53, P21, ALOX12, VEGF, MDA, GSH. Molecular marker impact upon AngII-induced ferroptosis was evaluated with students’ t-test，one-way analysis of variance (ANOVA).Results: As the concentration of Ang II increased，the level of ALOX12, P53, GSH and MDA increased in HUVECs. The expression of VEGFA in HUVECs is negatively correlated with dose of Ang II. Incubation of HUVECs in AngII and valsartan for 48hr reduces ALOX12, P21, GSH and MDA. Compared with the single AngII group, ALOX12, P21, GSH and MDA in valsartan group was decreased significantly（p=0.000）. In pifithrin-α hydrobromide-treated, ALOX12, P21, GSH and MDA was reduced significantly, as compared to valsartan group（p=0.000）. The most larger reduction in ALOX12, P21,GSH and MDA was pifithrin - α hydrobromide combined with valsartan group. In contrast, the expression of VEGFA increased significantly after HUVECs were treated with pifithrin - α hydrobromide and valsartan（p=0.000）.Conclusions: AngII can induce ferroptosis of vascular endothelial cells in a dose-dependent manner. The mechanism of AngII-induced ferroptosis may be regulated through the signal axis of ATR1,2-p53-ALOX12.

Biomechanical interactions of Schistosoma mansoni eggs with vascular endothelial cells facilitate egg extravasation

2021 ◽  
Author(s):  
Yi-Ting Yeh ◽  
Danielle E. Skinner ◽  
Ernesto Criado-Hidalgo ◽  
Natalie Shee Chen ◽  
Antoni Garcia-De Herreros ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Schistosoma Mansoni ◽  
Disease Transmission ◽  
Vascular Endothelial Cells ◽  
Flexible Substrate ◽  
Blood Stream ◽  
The Body ◽  
Dependent Manner ◽  
Vascular Endothelial ◽  
Maturation State

AbstractThe eggs of the parasitic blood fluke, Schistosoma, are the main drivers of the chronic pathologies associated with schistosomiasis, a disease of poverty afflicting approximately 220 million people worldwide. Eggs laid by Schistosoma mansoni in the bloodstream of the host are encapsulated by vascular endothelial cells (VECs), the first step in the migration of the egg from the blood stream into the lumen of the gut and eventual exit from the body. The biomechanics associated with encapsulation and extravasation of the egg are poorly understood. We demonstrate that S. mansoni eggs induce VECs to form two types of membrane extensions during encapsulation; filopodia that probe eggshell surfaces and intercellular nanotubes that presumably facilitate VEC communication. Encapsulation efficiency, the number of filopodia and intercellular nanotubes, and the length of these structures depend on the egg’s vitality and, to a lesser degree, its maturation state. During encapsulation, live eggs induce VEC contractility and membranous structures formation, in a Rho/ROCK pathway-dependent manner. Using elastic hydrogels embedded with fluorescent microbeads as substrates to culture VECs, live eggs induce VECs to exert significantly greater contractile forces during encapsulation than dead eggs, which leads to 3D deformations on both the VEC monolayer and the flexible substrate underneath. These significant mechanical deformations cause the VEC monolayer tension to fluctuate with eventual rupture of VEC junctions, thus facilitating egg transit out of the blood vessel. Overall, our data on the mechanical interplay between host VECs and the schistosome egg improve our understanding of how this parasite manipulates its immediate environment to maintain disease transmission.

scholarly journals Citrus bergamiaRisso Elevates Intracellular Ca2+in Human Vascular Endothelial Cells due to Release of Ca2+from Primary Intracellular Stores

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Purum Kang ◽  
Seung Ho Han ◽  
Hea Kyung Moon ◽  
Jeong-Min Lee ◽  
Hyo-Keun Kim ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Channel Blocker ◽  
Vascular Endothelial Cells ◽  
Umbilical Vein ◽  
Dependent Manner ◽  
Vascular Endothelial ◽  
Concentration Dependent Manner ◽  
Carbonyl Cyanide ◽  
Intracellular Ca ◽  
Umbilical Vein Endothelial Cells

The purpose of the present study is to examine the effects of essential oil ofCitrus bergamiaRisso (bergamot, BEO) on intracellular Ca2+in human umbilical vein endothelial cells. Fura-2 fluorescence was used to examine changes in intracellular Ca2+concentration[Ca2+]i. In the presence of extracellular Ca2+, BEO increased[Ca2+]i, which was partially inhibited by a nonselective Ca2+channel blocker La3+. In Ca2+-free extracellular solutions, BEO increased[Ca2+]iin a concentration-dependent manner, suggesting that BEO mobilizes intracellular Ca2+. BEO-induced[Ca2+]iincrease was partially inhibited by a Ca2+-induced Ca2+release inhibitor dantrolene, a phospholipase C inhibitor U73122, and an inositol 1,4,5-triphosphate (IP3)-gated Ca2+channel blocker, 2-aminoethoxydiphenyl borane (2-APB). BEO also increased[Ca2+]iin the presence of carbonyl cyanide m-chlorophenylhydrazone, an inhibitor of mitochondrial Ca2+uptake. In addition, store-operated Ca2+entry (SOC) was potentiated by BEO. These results suggest that BEO mobilizes Ca2+from primary intracellular stores via Ca2+-induced and IP3-mediated Ca2+release and affect promotion of Ca2+influx, likely via an SOC mechanism.

scholarly journals TB-4 Antitumor effects of a novel curcumin derivative curcumin monoglucuronide on glioblastoma cells in vitro and in vivo

2021 ◽  
Vol 3 (Supplement_6) ◽  
pp. vi6-vi6
Author(s):  
Takashi Fujii ◽  
Shun Yamamuro ◽  
Masamichi Takahashi ◽  
Akihide Kondo ◽  
Yoshitaka Narita ◽  
...  
Keyword(s):  
Cell Death ◽  
Water Soluble ◽  
Dependent Manner ◽  
Antitumor Effects ◽  
Multiple Cell ◽  
Human Gbm ◽  
Dose Dependent ◽  
Novel Therapeutic

Abstract The therapeutic outcome of glioblastomas (GBMs) is still very poor. Therefore, invention of novel therapeutic methods against GBM cases is considered urgent. The antitumor effects of naturally-derived compounds are attracting attention recently, and therapeutic efficacy of curcumin, a plant-derived compound previously used for multiple purpose, has been indicated in many cancer systems; however, clinical application of curcumin is considered difficult because of its poor bioavailability (under 1 %). Curcumin monoglucuronide (CMG), a water-soluble prodrug of curcumin recently developed for overcoming this weakness, has been demonstrated excellent antitumor effects for several malignancies in vitro and in vivo; therefore, we investigated the effects of CMG against GBM cells. CMG induced cell death of human GBM cells lines (T98G, U251MG, and U87MG) by dose dependent manner by triggering multiple forms of cell death such as apoptosis and perthanatos. Immunoblotting of CMG-treated GBM cell lysates demonstrated activation of multiple cell death signaling. Furthermore, immunodeficiency mice harboring intracerebral U87MG cell xenografts systemically treated by CMG showed significantly prolonged survival compared with control mice. These results suggest CMG would be a novel therapeutic agent against GBM cases.

scholarly journals GAS6 Inhibits Granulocyte Adhesion to Endothelial Cells

Blood ◽  
1998 ◽  
Vol 91 (7) ◽  
pp. 2334-2340
Author(s):  
Gian Carlo Avanzi ◽  
Margherita Gallicchio ◽  
Flavia Bottarel ◽  
Loretta Gammaitoni ◽  
Giuliana Cavalloni ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Vascular Endothelial Cells ◽  
Platelet Activating Factor ◽  
Polymorphonuclear Cells ◽  
Vascular Endothelial ◽  
Tnf Α ◽  
High Concentrations ◽  
Adhesive Interactions ◽  
Factor Α ◽  
Dose Dependent

GAS6 is a ligand for the tyrosine kinase receptors Rse, Axl, and Mer, but its function is poorly understood. Previous studies reported that both GAS6 and Axl are expressed by vascular endothelial cells (EC), which play a key role in leukocyte extravasation into tissues during inflammation through adhesive interactions with these cells. The aim of this work was to evaluate the GAS6 effect on the adhesive function of EC. Treatment of EC with GAS6 significantly inhibited adhesion of polymorphonuclear cells (PMN) induced by phorbol 12-myristate 13-acetate (PMA), platelet-activating factor (PAF), thrombin, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), but not that induced by FMLP and IL-8. GAS6 did not affect adhesion to resting EC. Titration experiments showed that high concentrations of GAS6 were needed to inhibit PMN adhesion and that inhibition was dose-dependent at the concentration range of 0.1 to 1 μg/mL. One possibility was that high concentrations were needed to overwhelm the effect of endogenous GAS6 produced by EC. In line with this possibility, treatment of resting EC with soluble Axl significantly potentiated PMN adhesion. Analysis of localization of GAS6 by confocal microscopy and cytofluorimetric analysis showed that it is concentrated along the plasma membrane in resting EC and treatment with PAF induces depletion and/or redistribution of the molecule. These data suggest that GAS6 functions as a physiologic antiinflammatory agent produced by resting EC and depleted when proinflammatory stimuli turn on the proadhesive machinery of EC.

scholarly journals Exchange Protein Directly Activated by cAMP Modulates Ebola Virus Uptake into Vascular Endothelial Cells

Viruses ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 563 ◽  
Author(s):  
Aleksandra Drelich ◽  
Barbara Judy ◽  
Xi He ◽  
Qing Chang ◽  
Shangyi Yu ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Ebola Virus ◽  
Vascular Endothelial Cells ◽  
Ex Vivo ◽  
Marburg Virus ◽  
Dependent Manner ◽  
Vascular Endothelial ◽  
Ultrastructural Studies ◽  
Ebov Infection ◽  
Exchange Protein

Members of the family Filoviridae, including Ebola virus (EBOV) and Marburg virus (MARV), cause severe hemorrhagic fever in humans and nonhuman primates. Given their high lethality, a comprehensive understanding of filoviral pathogenesis is urgently needed. In the present studies, we revealed that the exchange protein directly activated by cAMP 1 (EPAC1) gene deletion protects vasculature in ex vivo explants from EBOV infection. Importantly, pharmacological inhibition of EPAC1 using EPAC-specific inhibitors (ESIs) mimicked the EPAC1 knockout phenotype in the ex vivo model. ESI treatment dramatically decreased EBOV infectivity in both ex vivo vasculature and in vitro vascular endothelial cells (ECs). Furthermore, postexposure protection of ECs against EBOV infection was conferred using ESIs. Protective efficacy of ESIs in ECs was observed also in MARV infection. Additional studies using a vesicular stomatitis virus pseudotype that expresses EBOV glycoprotein (EGP-VSV) confirmed that ESIs reduced infection in ECs. Ultrastructural studies suggested that ESIs blocked EGP-VSV internalization via inhibition of macropinocytosis. The inactivation of EPAC1 affects the early stage of viral entry after viral binding to the cell surface, but before early endosome formation, in a phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)-dependent manner. Our study delineated a new critical role of EPAC1 during EBOV uptake into ECs.

Induction of Apoptotic Cell Death in Vascular Endothelial Cells Cultured in Three-Dimensional Collagen Lattice

1999 ◽  
Vol 248 (2) ◽  
pp. 498-508 ◽  
Author(s):  
Masafumi Kuzuya ◽  
Shosuke Satake ◽  
Miguel A. Ramos ◽  
Shigeru Kanda ◽  
Teruhiko Koike ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Death ◽  
Vascular Endothelial Cells ◽  
Apoptotic Cell ◽  
Three Dimensional ◽  
Apoptotic Cell Death ◽  
Vascular Endothelial ◽  
Collagen Lattice ◽  
Cells Cultured

Function of Tissue-type Plasminogen Activator Releaser on Vascular Endothelial Cells and Thrombolysis In Vivo

2002 ◽  
Vol 87 (06) ◽  
pp. 1069-1074 ◽  
Author(s):  
Hiroyuki Matsuno ◽  
Mikio Hayashi ◽  
Koji Horibuchi ◽  
Kiyotaka Okada ◽  
Hideharu Fukao ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Vascular Endothelial Cells ◽  
Tissue Type ◽  
Vascular Endothelial ◽  
Thrombosis Model ◽  
Artery Thrombosis ◽  
Type Plasminogen Activator ◽  
Thrombolytic Effect ◽  
Dose Dependent

SummaryThe effect of monosodium[2-(6-hydroxynaphthalen-2-yl)-6-methylpyrimidin-4-yloxy]acetate dihydrate (JTV-926) on fibrinolysis was investigated in vitro and in vivo. JTV-926 released tissue-type plasminogen activator (t-PA) from human vascular endothelial cells in a dose-dependent manner. The thrombolytic effect of JTV-926 was studied using three animal thrombosis models; a photo-irradiation-induced mouse carotid artery thrombosis model, a photo-irradiation-induced rat femoral artery thrombosis model and a thrombin-induced rat venous thrombosis model. In the mouse thrombosis model, t-PA deficient mice (t-PA−/−mice) and their wild-type (t-PA+/+) were used. JTV-926 was injected as a bolus 30 min after the interruption of blood flow by an occlusion thrombi. Blood flow was continuously monitored for 180 min after intravenous administration of JTV-926 (1 mg/kg). Although the recanalization rate of the occluded artery was 37.5% in t-PA +/+ mice with the vehicle control, it increased to 75% in t-PA+/+ mice after JTV-926 administration. However, when JTV-926 was administrated in t-PA−/−mice, vascular recanalization was not observed in any arteries. In the photo-irradiation-induced rat femoral artery thrombosis model, intra-duodenal administration of JTV-926 induced thrombolysis. Moreover, in the thrombin-induced rat venous thrombosis model, the dose-dependent thrombolysis was also observed by oral administration of JTV-926. It was suggested that JTV-926 revealed a sufficient thrombolytic effect through the absorption from the intestine. Thus, a newly synthesized compound, JTV-926 induced t-PA release from vascular endothelial cells and effective thrombolysis in vivo.

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