title: Transient supplementation of superoxide dismutase protects endothelial cells against Plasmodium falciparum-induced oxidative stress.
abstract: The pathogenesis of cerebral malaria, a major complication of Plasmodium falciparum infection, relies on mechanisms such as cytokine production and cytoadherence of parasitized red blood cells (PRBCs) on microvascular endothelial cells. In this way parasites avoid spleen clearance by sequestration in post-capillary venules of various organs including the brain. Infected erythrocytes adhesion has also been shown to have molecular signaling consequences providing insight on how tissue homeostasis could be comprised by endothelium perturbation. Our previous work demonstrated that PRBCs adhesion to human lung endothelial cells (HLEC) induces caspases activation, oxidative stress and apoptosis. Cytoplasmic Cu/Zn superoxide dismutase (SOD1), which provides the first line of defense against oxidative stress within a cell, is now used as a treatment of numerous diseases including traumatic brain injury and ischemic stroke. In this report, we demonstrated that transient supplementation of SOD1 protects endothelial cells against P. falciparum induced oxidative stress and apoptosis. We also showed a significant decrease in PRBCs cytoadherence through a downregulation of ICAM-1 and an induction of iNOS. Protection of endothelium via antioxidant delivery may constitute a relevant strategy in cerebral malaria treatment.
authors.affiliation: INSERM UMR511, Immunobiologie Cellulaire et Moléculaire des Infections Parasitaires, CHU Pitié-Salpêtrière, Université Pierre et Marie Curie, 91 bd de l'Hôpital, 75013 Paris, France. zacharie.taoufiq@etu.upmc.fr
authors.forename: Zacharie
authors.initials: Z
authors.lastname: Taoufiq
authors.forename: Paco
authors.initials: P
authors.lastname: Pino
authors.forename: Nathalie
authors.initials: N
authors.lastname: Dugas
authors.forename: Marc
authors.initials: M
authors.lastname: Conti
authors.forename: Maurel
authors.initials: M
authors.lastname: Tefit
authors.forename: Dominique
authors.initials: D
authors.lastname: Mazier
authors.forename: Ioannis
authors.initials: I
authors.lastname: Vouldoukis
mesh_terms: D000818:Animals; D017209:Apoptosis; D002417:Cattle; D002448:Cell Adhesion; D002469:Cell Separation; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004912:Erythrocytes / Q000469:parasitology; D015696:Gene Products, tat / Q000235:genetics; D006801:Humans; D006861:Hydrogen Peroxide; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008168:Lung / Q000166:cytology; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D018384:Oxidative Stress; D010963:Plasmodium falciparum / Q000502:physiology*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D000072105:Superoxide Dismutase-1; D014162:Transfection
chemical_list: D015696:Gene Products, tat; C000606290:SOD1 protein, human; D018799:Intercellular Adhesion Molecule-1; D006861:Hydrogen Peroxide; D052248:Nitric Oxide Synthase Type I; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1