title: Dietary anthocyanins protect endothelial cells against peroxynitrite-induced mitochondrial apoptosis pathway and Bax nuclear translocation: an in vitro approach.
abstract: Anthocyanins have received increasing attention because of their relatively high intake in humans and wide range of potential health-promoting effects, including anti-atherogenic properties. Evidences support their vascular protective effects but the involved molecular mechanisms have not been well clarified. The endothelium seems to have a central role in atherogenesis and apoptosis is emerging as a crucial event in this disease progression. Following our previous work on the biochemical pathways underlying peroxynitrite-triggered apoptosis in endothelial cells, here we investigated potential mechanisms responsible for the cytoprotective actions of three common anthocyanins, namely cyanidin- delphinidin- and pelargonidin-3-glucoside, against this process. Beyond their antioxidant properties, all these flavonoids, possessing either catecholic or monophenolic structures, were able to counteract peroxynitrite-induced apoptotic effects in endothelial cells through the inhibition of several crucial signaling cascades. Actually, pre-incubation of cells with 25 μM anthocyanins prevented them from peroxynitrite-mediated apoptosis, which was evaluated by the loss of mitochondrial membrane potential, caspases-9 and-3 activation, the increase in cytoplasmatic Bax levels and the inactivation of the PI3 K/Akt pathway. Moreover, they counteracted the translocation of Bax into the nucleus, as observed by immunocytochemistry and immunoblot, an event shown for the first time in endothelial cells apoptotic process. Such cellular actions could not be inferred from their in vitro antioxidant properties. These results suggest a potential role of dietary anthocyanins in the modulation of several apoptotic signaling pathways triggered by peroxynitrite in endothelial cells, supporting mechanistically their health benefits in the context of prevention of endothelial dysfunction and, ultimately, of atherosclerosis.
authors.affiliation: Faculty of Pharmacy, University of Coimbra, Polo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548, Coimbra, Portugal.
authors.forename: Joana
authors.initials: J
authors.lastname: Paixão
authors.forename: Teresa C P
authors.initials: TC
authors.lastname: Dinis
authors.forename: Leonor M
authors.initials: LM
authors.lastname: Almeida
mesh_terms: D000818:Animals; D000872:Anthocyanins / Q000494:pharmacology*; D001011:Aorta / Q000166:cytology; D017209:Apoptosis / Q000187:drug effects*; D061945:Caspase Inhibitors; D002417:Cattle; D004730:Endothelium, Vascular / Q000166:cytology*; D004789:Enzyme Activation / Q000187:drug effects; D005960:Glucosides / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D030421:Peroxynitrous Acid / Q000378:metabolism / Q000494:pharmacology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D021381:Protein Transport / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
chemical_list: D000872:Anthocyanins; D061945:Caspase Inhibitors; D005960:Glucosides; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; C462279:cyanidin-3-O-beta-glucopyranoside; D030421:Peroxynitrous Acid; C494120:delphinidin 3-O-glucopyranoside; C078485:pelargonidin-3-glucoside; D051057:Proto-Oncogene Proteins c-akt