Plans: “Post-translational Oxidative Modification of Vascular Proteins in Key Antioxidant Deficiency States,” the title of project 11, summarizes the research direction.<\/p>\n
In vitro<\/em> studies to characterize oxidant stress in G6PD-deficient cell lines have been completed. Specifically, both G6PD-deficient cell lines, under basal conditions, exhibit similar indices of oxidant stress as control cells; however, when challenged with an oxidant, G6PD-deficient cell lines demonstrate increased indices of oxidant stress. Researchers challenged G6PD-deficient and control cell lines with hydrogen peroxide and demonstrated increased reactive oxygen species production and peroxynitrite formation as well as decreased indices of glutathione recycling as compared to control cells. In addition, they found that the effect partially could be reversed with the administration of antioxidant agents. In a second series of experiments, researchers challenged control cells with aldosterone (10-9 to 10-7 M). They selected this agent because it has been reported to cause an oxidative vasculopathy in humans and hypothesized that this occurred due to a down-regulation in G6PD activity. Researchers found that bovine aortic endothelial cells treated with aldosterone demonstrated a concentration-dependent decrease in G6PD expression, activity and NADPH levels. This, in turn, led to an increase in reactive oxygen species production, peroxynitrite formation, and a decrease in glutathione stores. These effects were blocked by an inhibitor of the mineralocorticoid receptor, spironolactone.<\/p>\n Researchers then isolated tissues from wild-type and age-matched G6PD-deficient hemizygous male mice. They found that under basal conditions, hepatic and vascular tissues harvested from the G6PD-deficient mice demonstrate increased reactive oxygen species and decreased glutathione stores compared to the wild-type controls. They also found that when challenged with hydrogen peroxide ex vivo, the tissues exhibit exaggerated reactive oxygen species and peroxynitrite formation. Researchers infused wild-type mice with aldosterone (50 \u00b5g\/kg\/day) for 14 days and found that this decreases G6PD expression, activity, and NADPH levels in the aorta rendering mice with a normal G6PD genotype G6PD-deficient. This effect is associated with a decrease in glutathione stores and an increase in reactive oxygen species production, glutathione levels, and peroxynitrite formation, all of which may be restored to basal levels by co-administration of spironolactone (a mineralocorticoid receptor blocker) or over-expression of G6PD.<\/p>\n","protected":false},"excerpt":{"rendered":" Plans: “Post-translational Oxidative Modification of Vascular Proteins in Key Antioxidant Deficiency States,” the title of project 11, summarizes the research direction. In vitro studies to characterize oxidant stress in G6PD-deficient cell lines have been completed. Specifically, both G6PD-deficient cell lines, under basal conditions, exhibit similar indices of oxidant stress as control cells; however, when challenged […]<\/p>\n","protected":false},"author":2,"featured_media":0,"parent":0,"menu_order":88,"comment_status":"closed","ping_status":"closed","template":"","meta":[],"_links":{"self":[{"href":"https:\/\/www.bumc.bu.edu\/cardiovascularproteomics\/wp-json\/wp\/v2\/pages\/69"}],"collection":[{"href":"https:\/\/www.bumc.bu.edu\/cardiovascularproteomics\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/www.bumc.bu.edu\/cardiovascularproteomics\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/www.bumc.bu.edu\/cardiovascularproteomics\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.bumc.bu.edu\/cardiovascularproteomics\/wp-json\/wp\/v2\/comments?post=69"}],"version-history":[{"count":8,"href":"https:\/\/www.bumc.bu.edu\/cardiovascularproteomics\/wp-json\/wp\/v2\/pages\/69\/revisions"}],"predecessor-version":[{"id":1929,"href":"https:\/\/www.bumc.bu.edu\/cardiovascularproteomics\/wp-json\/wp\/v2\/pages\/69\/revisions\/1929"}],"wp:attachment":[{"href":"https:\/\/www.bumc.bu.edu\/cardiovascularproteomics\/wp-json\/wp\/v2\/media?parent=69"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}