Protective role of malvidin-3-glucoside on peroxynitrite-induced damage in endothelial cells by counteracting reactive species formation and apoptotic mitochondrial pathway.
The health-promoted benefits of anthocyanins, including vascular protective effects and antiatherogenic properties, have now been recognized, but the involved molecular mechanisms have not been well elucidated. Following our previous work on cytoprotective mechanisms of some anthocyanins against apoptosis triggered by peroxynitrite in endothelial cells, here we investigated the protective role of malvidin-3-glucoside, a major dietary anthocyanin, on such deleterious process, by exploring the interference on cellular reactive species formation and on apoptotic mitochondrial pathway. Preincubation of cells with 25 μM malvidin-3-glucoside protected efficiently endothelial cells from peroxynitrite-promoted apoptotic death, an effect which may be partially mediated by its ability to decrease the formation of reactive species after cell aggression, as assessed by the dichlorodihydrofluorescein diacetate assay and by carbonyl groups formation. Moreover, malvidin-3-glucoside inhibited mitochondrial apoptotic signaling pathways induced by peroxynitrite, by counteracting mitochondrial membrane depolarization, the activation of caspase-3 and -9, and the increase in the expression of the proapoptotic Bax protein. Altogether, our data expands our knowledge about the molecular mechanisms underlying the vascular protection afforded by malvidin-3-glucoside, and anthocyanins in general, in the context of prevention of endothelial dysfunction and atherosclerosis.
Center for Neuroscience and Cell Biology (CNC), University of Coimbra, 3004-517 Coimbra, Portugal.
Joana
J
Paixão
Teresa C P
TC
Dinis
Leonor M
LM
Almeida
D000818:Animals; D000872:Anthocyanins / Q000737:chemistry / Q000494:pharmacology*; D001011:Aorta / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D004789:Enzyme Activation / Q000187:drug effects; D016166:Free Radical Scavengers / Q000494:pharmacology; D005960:Glucosides; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D030421:Peroxynitrous Acid / Q000633:toxicity*; D020011:Protective Agents / Q000737:chemistry / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012235:Rhodamines / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000872:Anthocyanins; D016166:Free Radical Scavengers; D005960:Glucosides; D020011:Protective Agents; D017382:Reactive Oxygen Species; D012235:Rhodamines; D051028:bcl-2-Associated X Protein; C058319:dihydrorhodamine 123; D030421:Peroxynitrous Acid; C458419:malvidin-3-glucoside; D053148:Caspase 3; D053453:Caspase 9