Fullerene Nanoparticles Selectively Enter Oxidation-Damaged Cerebral Microvessel Endothelial Cells and Inhibit JNK-Related Apoptosis

Abstract

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.

Modulation of Adenosine Receptors by [60]Fullerene Hydrosoluble Derivative in SK-N-MC Cells

“…Consequently, C 60 (C(COOH) 2 ) 2 treatment could regulate several downstream signaling events, including reduced activation of transcription factor c-Jun and caspase-3 and inhibition of PARP cleavage and mitochondrial cytochrome c release. 43 Effector mechanisms other than the classical adenylate cyclase and phospholipase C mediated pathways are associated with the stimulation of adenosine receptors. For example, adenosine action can activate phosphoinositide 3-kinase (PI3K), mitogenactivated protein kinases (MAPKs), and extracellular receptor signal-induced kinase (ERK).…”

Central nervous system toxicity of metallic nanoparticles

“…132 Compared to unmodified fullerene NPs, which can generate ROS to damage cells, surface-modified fullerene NPs can selectively enter oxidized cerebral microvessel endothelial cells and protect these cells by attenuating ROS-induced cellular damage, such as F-actin depolymerization. 133,134 Nanocrystalline TiO 2 is widely applied in biomedical ceramics and implant-related biomaterials that are translocated into the murine brain, induce pathological lesions to the hippocampus, and alter neurochemical levels in the brain after intranasal instillation. 135,136 However, the neurotoxicity of nanocrystalline TiO 2 could be affected by surface modification.…”

Nanocomposite and Nanostructured Carbon-based Films as Growth Substrates for Bone Cells

“…This is due to the relatively large number of conjugated double bonds in the fullerene molecule, which can be attacked by radical species. Thus, fullerenes would be suitable for applications in quenching oxygen radicals, and thus preventing inflammatory and allergic reactions (Dellinger et al, 2009) and damage of various tissues and organs, including the lung (Chen et al, 2004), blood vessels (Maeda et al, 2008) and brain (Tykhomyrov et al, 2008;Lao et al, 2009). Fullerenes also protected epithelial cells in vitro from anoikis, i.e., apoptosis due to adhesion deprivation, by a mechanism supporting the formation of focal adhesion plaques, assembly of the actin cytoskeleton and cell spreading, which was also attributed to the antioxidative action of fullerenes (Straface et al, 1999).…”