A water-soluble fullerene vesicle alleviates angiotensin II-induced oxidative stress in human umbilical venous endothelial cells.
A water-soluble fullerene vesicle based on the Buckminsterfullerene molecule (Ph(5)C(60)K, denoted as PhK) was explored to determine its effects on anti-oxidation of human umbilical endothelial cells (HUVEC) exposed to exogenous and endogenous reactive oxygen species (ROS). Hydrogen peroxide 0.05-0.25 mmol/L remarkably reduced the cellular viability of HUVEC. This reduction in viability was markedly improved when PhK 0.01-1 micromol/L was added simultaneously to the culture medium. The reduction of viability in HUVEC induced by angiotensin II (AII) 10(-9) to 10(-7) mol/L was improved by pretreatment with PhK 0.1 or 10 micromol/L 12 h before AII stimulation. The ROS indicator CM-H(2)DCFDA demonstrated the efficacy of PhK 1 or 10 micromol/L in decreasing AII-induced ROS production to the level induced by the AII receptor blocker RNH-6470 20 micromol/L. The AII-induced peroxynitrite formation, as gauged using hydroxyphenyl fluorescein as a probe, was alleviated significantly by either pretreatment with PhK 0.1 or 1 micromol/L. Electron microscopy revealed intracellular localization of PhK in HUVEC after 12 h incubation. The PhK decreased the AII-induced apoptosis and lipid peroxidation processes as revealed by hexanoyl-lysine adduct formation. These observations show that the PhK water-soluble fullerene vesicle is promising as a compound controlling not only exogenous ROS, but also endogenous AII-mediated pathophysiological conditions.
Maeda
Rui
R
Center for NanoBio Integration, The University of Tokyo, Japan.
Noiri
Eisei
E
Isobe
Hiroyuki
H
Homma
Tatsuya
T
Tanaka
Tamami
T
Negishi
Kousuke
K
Doi
Kent
K
Fujita
Toshiro
T
Nakamura
Eiichi
E
D000328:Adult; D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D019793:Fluorescein; D005452:Fluoresceins; D005456:Fluorescent Dyes; D037741:Fullerenes / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D017665:Hydroxyl Radical / Q000378:metabolism; D007150:Immunohistochemistry; D046529:Microscopy, Electron, Transmission; D016877:Oxidants / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D030421:Peroxynitrous Acid / Q000096:biosynthesis; D011247:Pregnancy; D017382:Reactive Oxygen Species / Q000378:metabolism; D012995:Solubility; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D005452:Fluoresceins; D005456:Fluorescent Dyes; D037741:Fullerenes; D016877:Oxidants; D017382:Reactive Oxygen Species; C543635:hydroxyphenyl fluoroscein; D000804:Angiotensin II; D030421:Peroxynitrous Acid; D017665:Hydroxyl Radical; D019793:Fluorescein