Oxidative Stress and Neurodegeneration Group

Ciudad Real, Spain

Oxidative Stress and Neurodegeneration Group

Ciudad Real, Spain
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Duran-Prado M.,University of Castilla - La Mancha | Duran-Prado M.,Oxidative Stress and Neurodegeneration Group | Frontinan J.,University of Castilla - La Mancha | Frontinan J.,Oxidative Stress and Neurodegeneration Group | And 11 more authors.
PLoS ONE | Year: 2014

Neuropathological symptoms of Alzheimer's disease appear in advances stages, once neuronal damage arises. Nevertheless, recent studies demonstrate that in early asymptomatic stages, β-amyloid peptide damages the cerebral microvasculature through mechanisms that involve an increase in reactive oxygen species and calcium, which induces necrosis and apoptosis of endothelial cells, leading to cerebrovascular dysfunction. The goal of our work is to study the potential preventive effect of the lipophilic antioxidant coenzyme Q (CoQ) against β-amyloid-induced damage on human endothelial cells. We analyzed the protective effect of CoQ against Aβ-induced injury in human umbilical vein endothelial cells (HUVECs) using fluorescence and confocal microscopy, biochemical techniques and RMN-based metabolomics. Our results show that CoQ pretreatment of HUVECs delayed Aβ incorporation into the plasma membrane and mitochondria. Moreover, CoQ reduced the influx of extracellular Ca2+, and Ca2+ release from mitochondria due to opening the mitochondrial transition pore after b-amyloid administration, in addition to decreasing O2 .- and H2O2 levels. Pretreatment with CoQ also prevented β-amyloid-induced HUVECs necrosis and apoptosis, restored their ability to proliferate, migrate and form tube-like structures in vitro, which is mirrored by a restoration of the cell metabolic profile to control levels. CoQ protected endothelial cells from Aβ-induced injury at physiological concentrations in human plasma after oral CoQ supplementation and thus could be a promising molecule to protect endothelial cells against amyloid angiopathy. © 2014 Durán-Prado et al.

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