Fullerene nanoparticles selectively enter oxidation-damaged cerebral microvessel endothelial cells and inhibit JNK-related apoptosis.
There is a dearth in fundamental cellular-level understanding of how nanoparticles interact with the cells of the blood brain barrier (BBB), particularly under the oxidative environment. The apoptosis of cerebral microvessel endothelial cells (CMECs) induced by oxidative stress injury plays a key role in the dysfunction of BBB. By use of CMECs as an in vitro BBB model, we show for the first time that C(60)(C(COOH)(2))(2) nanoparticles can selectively enter oxidized CMECs rather than normal cells, and maintain CMECs integrity by attenuating H(2)O(2)-induced F-actin depolymerization via the observation of several state-of-the art microscopic techniques. Additionally, we have found that C(60)(C(COOH)(2))(2) nanoparticles greatly inhibit the apoptosis of CMECs induced by H(2)O(2), which is related to their modulation of the JNK pathway. C(60)(C(COOH)(2))(2) nanoparticles can regulate several downstream signaling events related to the JNK pathway, including reduction of JNK phosphorylation, activation of activator protein 1 (AP-1) and caspase-3, and inhibition of polyADP-ribose polymerase (PARP) cleavage and mitochondrial cytochrome c release. Our results indicate that C(60)(C(COOH)(2))(2) nanoparticles possess a novel ability of selectively entering oxidation-damaged cerebral endothelial cells rather than normal endothelial cells and then protecting them from apoptosis.
CAS Key Lab for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing, China.
Fang
F
Lao
Long
L
Chen
Wei
W
Li
Cuicui
C
Ge
Ying
Y
Qu
Quanmei
Q
Sun
Yuliang
Y
Zhao
Dong
D
Han
Chunying
C
Chen
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001692:Biological Transport; D001921:Brain / Q000098:blood supply*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D037741:Fullerenes / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D048670:MAP Kinase Kinase 4 / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D055806:Microvessels / Q000166:cytology*; D037742:Nanotubes, Carbon / Q000737:chemistry; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013379:Substrate Specificity
D037741:Fullerenes; D037742:Nanotubes, Carbon; D006861:Hydrogen Peroxide; D048670:MAP Kinase Kinase 4; C069837:fullerene C60