Fullerene nanoparticles selectively enter oxidation-damaged cerebral microvessel endothelial cells inhibit JNK-related apoptosis

摘要

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_2O_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_2O_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.