Adverse effects of fullerenes on endothelial cells: Fullerenol C60(OH)24 induced tissue factor and ICAM-1 membrane expression and apoptosis in vitro

Adverse effects of fullerenes on endothelial cells: Fullerenol C60(OH)24 induced tissue factor and ICAM-1 membrane expression and apoptosis in vitro

Monique P Gelderman1, Olga Simakova2, Jeffrey D Clogston3, Anil K Patri3, Sheena F Siddiqui1, Alexander C Vostal1, Jan Simak11CBER, FDA, Rockville, MD, USA; 2School of Medicine, USUHS, Bethesda, MD, USA; 3Nanotechnology Characterization Lab, Advanced Technology Program, SAIC-Frederick, Frederick, Ma...

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Autores principales: Monique P Gelderman, Olga Simakova, Jeffrey D Clogston, Anil K Patri, Sheena F Siddiqui, et al
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2008
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Medicine (General)
R5-920
Acceso en línea:https://doaj.org/article/98ec3433c80847bf919c872329341cbe
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spelling oai:doaj.org-article:98ec3433c80847bf919c872329341cbe2021-12-02T05:09:45ZAdverse effects of fullerenes on endothelial cells: Fullerenol C60(OH)24 induced tissue factor and ICAM-1 membrane expression and apoptosis in vitro1176-91141178-2013https://doaj.org/article/98ec3433c80847bf919c872329341cbe2008-03-01T00:00:00Zhttp://www.dovepress.com/adverse-effects-of-fullerenes-on-endothelial-cells-fullerenol-c60oh24--a736https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Monique P Gelderman1, Olga Simakova2, Jeffrey D Clogston3, Anil K Patri3, Sheena F Siddiqui1, Alexander C Vostal1, Jan Simak11CBER, FDA, Rockville, MD, USA; 2School of Medicine, USUHS, Bethesda, MD, USA; 3Nanotechnology Characterization Lab, Advanced Technology Program, SAIC-Frederick, Frederick, Maryland, USAAbstract: We studied the effects of a C60 water suspension at 4 µg/mL (nC60) and the water soluble fullerenol C60(OH)24 at final concentrations of 1—100 µg/mL on human umbilical vein endothelial cells (HUVECs) in culture. We found that a 24 hr treatment of HUVECs with C60(OH)24 at 100 µg/mL significantly increased cell surface expression of ICAM-1(CD54) (67 ± 4% CD54+ cells vs. 19 ± 2 % CD54+ cells in control; p < 0.001). In addition, this treatment induced the expression of tissue factor (CD142) on HUVECs (54 ± 20% CD142+ cells vs 4 ± 2% CD142+ cells in control; p = 0.008) and increased exposure of phosphatidylserine (PS) (29 ± 2% PS+ cells vs. 12 ± 5% PS+ cells in control; p < 0.001). Analysis of cell cycle and DNA fragmentation (TUNEL) showed that both nC60 and C60(OH)24 caused G1 arrest of HUVECs and C60(OH)24 induced significant apoptosis (21 ± 2% TUNEL+ cells at 100 µg/mL of C60(OH)24 vs. 4 ± 2% TUNEL+ cells in control; p < 0.001). We also demonstrated that both nC60 and C60(OH)24 induced a rapid concentration dependent elevation of intracellular calcium [Ca2+]i. This could be inhibited by EGTA, suggesting that the source of [Ca2+]i in fullerene stimulated calcium flux is predominantly from the extracellular environment. In conclusion, fullerenol C60OH)24 had both pro-inflammatory and pro-apoptotic effects on HUVECs, indicating possible adverse effects of fullerenes on the endothelium.Keywords: endothelial cells, fullerenes, tissue factor, apoptosis, ICAM-1, flow cytometry Monique P GeldermanOlga SimakovaJeffrey D ClogstonAnil K PatriSheena F Siddiquiet alDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2008, Iss Issue 1, Pp 59-68 (2008)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Monique P Gelderman
Olga Simakova
Jeffrey D Clogston
Anil K Patri
Sheena F Siddiqui
et al
Adverse effects of fullerenes on endothelial cells: Fullerenol C60(OH)24 induced tissue factor and ICAM-1 membrane expression and apoptosis in vitro
description Monique P Gelderman1, Olga Simakova2, Jeffrey D Clogston3, Anil K Patri3, Sheena F Siddiqui1, Alexander C Vostal1, Jan Simak11CBER, FDA, Rockville, MD, USA; 2School of Medicine, USUHS, Bethesda, MD, USA; 3Nanotechnology Characterization Lab, Advanced Technology Program, SAIC-Frederick, Frederick, Maryland, USAAbstract: We studied the effects of a C60 water suspension at 4 µg/mL (nC60) and the water soluble fullerenol C60(OH)24 at final concentrations of 1—100 µg/mL on human umbilical vein endothelial cells (HUVECs) in culture. We found that a 24 hr treatment of HUVECs with C60(OH)24 at 100 µg/mL significantly increased cell surface expression of ICAM-1(CD54) (67 ± 4% CD54+ cells vs. 19 ± 2 % CD54+ cells in control; p < 0.001). In addition, this treatment induced the expression of tissue factor (CD142) on HUVECs (54 ± 20% CD142+ cells vs 4 ± 2% CD142+ cells in control; p = 0.008) and increased exposure of phosphatidylserine (PS) (29 ± 2% PS+ cells vs. 12 ± 5% PS+ cells in control; p < 0.001). Analysis of cell cycle and DNA fragmentation (TUNEL) showed that both nC60 and C60(OH)24 caused G1 arrest of HUVECs and C60(OH)24 induced significant apoptosis (21 ± 2% TUNEL+ cells at 100 µg/mL of C60(OH)24 vs. 4 ± 2% TUNEL+ cells in control; p < 0.001). We also demonstrated that both nC60 and C60(OH)24 induced a rapid concentration dependent elevation of intracellular calcium [Ca2+]i. This could be inhibited by EGTA, suggesting that the source of [Ca2+]i in fullerene stimulated calcium flux is predominantly from the extracellular environment. In conclusion, fullerenol C60OH)24 had both pro-inflammatory and pro-apoptotic effects on HUVECs, indicating possible adverse effects of fullerenes on the endothelium.Keywords: endothelial cells, fullerenes, tissue factor, apoptosis, ICAM-1, flow cytometry
format article
author Monique P Gelderman
Olga Simakova
Jeffrey D Clogston
Anil K Patri
Sheena F Siddiqui
et al
author_facet Monique P Gelderman
Olga Simakova
Jeffrey D Clogston
Anil K Patri
Sheena F Siddiqui
et al
author_sort Monique P Gelderman
title Adverse effects of fullerenes on endothelial cells: Fullerenol C60(OH)24 induced tissue factor and ICAM-1 membrane expression and apoptosis in vitro
title_short Adverse effects of fullerenes on endothelial cells: Fullerenol C60(OH)24 induced tissue factor and ICAM-1 membrane expression and apoptosis in vitro
title_full Adverse effects of fullerenes on endothelial cells: Fullerenol C60(OH)24 induced tissue factor and ICAM-1 membrane expression and apoptosis in vitro
title_fullStr Adverse effects of fullerenes on endothelial cells: Fullerenol C60(OH)24 induced tissue factor and ICAM-1 membrane expression and apoptosis in vitro
title_full_unstemmed Adverse effects of fullerenes on endothelial cells: Fullerenol C60(OH)24 induced tissue factor and ICAM-1 membrane expression and apoptosis in vitro
title_sort adverse effects of fullerenes on endothelial cells: fullerenol c60(oh)24 induced tissue factor and icam-1 membrane expression and apoptosis in vitro
publisher Dove Medical Press
publishDate 2008
url https://doaj.org/article/98ec3433c80847bf919c872329341cbe
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AT jeffreydclogston adverseeffectsoffullerenesonendothelialcellsfullerenolc60oh24inducedtissuefactorandicam1membraneexpressionandapoptosisinvitro
AT anilkpatri adverseeffectsoffullerenesonendothelialcellsfullerenolc60oh24inducedtissuefactorandicam1membraneexpressionandapoptosisinvitro
AT sheenafsiddiqui adverseeffectsoffullerenesonendothelialcellsfullerenolc60oh24inducedtissuefactorandicam1membraneexpressionandapoptosisinvitro
AT etal adverseeffectsoffullerenesonendothelialcellsfullerenolc60oh24inducedtissuefactorandicam1membraneexpressionandapoptosisinvitro
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