Cyanidin-3-O-glucoside modulates intracellular redox status andprevents HIF-1 stabilization in endothelial cells in vitro exposed tochronic hypoxia

The term hypoxia refers to conditions characterized by a relative restriction of o xygen supply. It is usuallyassociated to a paradoxical overproduction of reactive oxygen species (ROS) and to the activation ofseveral transcription factors, including HIF-1 alpha, which in turn trigger angiogenic and apoptotic response. In this study we have investigated the mechanisms by which the anthocyanin cyanidin-3-O-glucoside(C3G) modulates hypoxia induced response in human endothelial cells (HUVECs). In fact, hypoxia inducesan increase of ROS generation in HUVECs paralleled by a loss of antioxidant cellular capacity. Accordingto the observed increase of HO-1 mRNA expression, pretreatment of C3G to HUVEC reduces the entityof oxidative stress thanks to the activation of cellular antioxidant response. C3G also attenuates HIF-1protein accumulation conditions supporting the hypothesis of a major role of oxidative stress in thepresence of low oxygen. Furthermore, the increased expression of angiogenesis and apoptosis markers(MMP-2 and caspase-3) due to HIF-1 alpha activation by hypoxia is reduced in C3G pretreated cells. Overall, our data suggest that the modulation of intracellular redox status induced by C3G may be animportant protective mechanism against endothelial damage in hypoxic conditions. (C) 2014 Elsevier Ireland Ltd. All rights reserved.