title: Vitamin B12 protects against superoxide-induced cell injury in human aortic endothelial cells.
abstract: Superoxide (O(2)(•-)) is implicated in inflammatory states including arteriosclerosis and ischemia-reperfusion injury. Cobalamin (Cbl) supplementation is beneficial for treating many inflammatory diseases and also provides protection in oxidative-stress-associated pathologies. Reduced Cbl reacts with O(2)(•-) at rates approaching that of superoxide dismutase (SOD), suggesting a plausible mechanism for its anti-inflammatory properties. Elevated homocysteine (Hcy) is an independent risk factor for cardiovascular disease and endothelial dysfunction. Hcy increases O(2)(•-) levels in human aortic endothelial cells (HAEC). Here, we explore the protective effects of Cbl in HAEC exposed to various O(2)(•-) sources, including increased Hcy levels. Hcy increased O(2)(•-) levels (1.6-fold) in HAEC, concomitant with a 20% reduction in cell viability and a 1.5-fold increase in apoptotic death. Pretreatment of HAEC with physiologically relevant concentrations of cyanocobalamin (CNCbl) (10-50nM) prevented Hcy-induced increases in O(2)(•-) and cell death. CNCbl inhibited both Hcy and rotenone-induced mitochondrial O(2)(•-) production. Similarly, HAEC challenged with paraquat showed a 1.5-fold increase in O(2)(•-) levels and a 30% decrease in cell viability, both of which were prevented with CNCbl pretreatment. CNCbl also attenuated elevated O(2)(•-) levels after exposure of cells to a Cu/Zn-SOD inhibitor. Our data suggest that Cbl acts as an efficient intracellular O(2)(•-) scavenger.
authors.affiliation: Integrative Medical Sciences, Northeastern Ohio Universities Colleges of Medicine and Pharmacy, Rootstown, OH 44272, USA.
authors.forename: Edward S
authors.initials: ES
authors.lastname: Moreira
authors.forename: Nicola E
authors.initials: NE
authors.lastname: Brasch
authors.forename: June
authors.initials: J
authors.lastname: Yun
mesh_terms: D001011:Aorta / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects; D050197:Atherosclerosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D019610:Cytoprotection; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D013481:Superoxides / Q000378:metabolism; D014805:Vitamin B 12 / Q000494:pharmacology*; D014803:Vitamin B Complex / Q000494:pharmacology*
chemical_list: D016166:Free Radical Scavengers; D013481:Superoxides; D014803:Vitamin B Complex; D014805:Vitamin B 12