title: Overexpression of copper/zinc superoxide dismutase decreases ischemia-like astrocyte injury.
abstract: Overexpression of copper/zinc superoxide dismutase (SOD1) in transgenic mice protects from transient focal cerebral ischemia in adult animals, but increases oxidative injury in perinatal mice. The effect of SOD1 overexpression on astrocytes subjected to ischemia-like insults has not yet been determined. Overexpression of human SOD1 in astrocytes resulted in a 3-fold increase in SOD1 activity without coupled up-regulation of catalase or glutathione peroxidase activities. Cells subjected to oxygen-glucose deprivation (OGD) or glucose deprivation to mimic ischemic injury were protected by SOD1 overexpression. OGD injury was reduced 47.6+/-9.3%, assessed by release of lactate dehydrogenase. OGD also caused a significant increase in catalase activity which was moderated by SOD1 overexpression. The level of glutathione in astrocytes overexpressing SOD1 was maintained at higher levels following 5 h OGD compared to control cultures under the same conditions. Reduction of glutathione prior to OGD significantly increased cell death of SOD1-overexpressing astrocytes as well as controls, but SOD1 still provided significant protection, suggesting that both GSH-dependent scavenging and GSH-independent scavenging are relevant to SOD1 protection in astrocytes.
authors.affiliation: Department of Anesthesia, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Joyce H
authors.initials: JH
authors.lastname: Ma
authors.forename: Rona G
authors.initials: RG
authors.lastname: Giffard
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000201:enzymology* / Q000473:pathology; D002545:Brain Ischemia / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D051379:Mice; D013482:Superoxide Dismutase / Q000378:metabolism*
chemical_list: D013482:Superoxide Dismutase