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Int J Nanomedicine ; 3(1): 59-68, 2008.
Article in English | MEDLINE | ID: mdl-18488416

ABSTRACT

We studied the effects of a C60 water suspension at 4 microg/mL (nC60) and the water soluble fullerenol C60(OH)24 at final concentrations of 1-100 microg/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 microg/mL significantly increased cell surface expression of ICAM-1(CD54) (67 +/- 4% CD54+ cells vs. 19 +/- 2 % CD540 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 microg/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 C60(OH)24 had both pro-inflammatory and pro-apoptotic effects on HUVECs, indicating possible adverse effects of fullerenes on the endothelium.


Subject(s)
Endothelial Cells/drug effects , Endothelial Cells/metabolism , Fullerenes/adverse effects , Intercellular Adhesion Molecule-1/metabolism , Thromboplastin/metabolism , Apoptosis/drug effects , Cell Membrane/drug effects , Cell Membrane/metabolism , Cell Survival/drug effects , Cells, Cultured , Dose-Response Relationship, Drug , Endothelial Cells/cytology , Gene Expression/drug effects , Humans
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