Copper/zinc superoxide dismutase transgenic brain accumulates hydrogen peroxide after perinatal hypoxia ischemia.
Unlike the mature animal, immature mice transgenic for copper/zinc superoxide dismutase (SOD1) have greater brain injury after hypoxia-ischemia than their wild-type nontransgenic littermates. To assess the role of oxidative stress in the pathogenesis of this injury, we measured histopathological damage, lipid peroxidation products, enzymatic activities of catalase and glutathione peroxidase, and hydrogen peroxide (H2O2) concentration in these animals before and after hypoxic-ischemic injury. Lipid peroxidation products were significantly increased 2 hours after the insult in both transgenic and nontransgenic brains in hippocampus, the most damaged brain region. Catalase activity did not increase in response to SOD1 overexpression or injury in either group. However, glutathione peroxidase activity, unchanged in response to overexpression, decreased significantly 24 hours after injury in both groups. At 24 hours after injury, greater H2O2 accumulation was observed in transgenic brains. Because SOD1 dismutates superoxide to H2O2, overexpression of SOD1 in the presence of developmentally low activities of the catalytic enzymes glutathione peroxidase and catalase leads to an increased production of H2O2, and may explain the increased brain injury observed after hypoxia-ischemia in neonatal SOD1 mice.
Fullerton
H J
HJ
Department of Neurology, University of California-San Francisco, 94143-0114, USA.
Ditelberg
J S
JS
Chen
S F
SF
Sarco
D P
DP
Chan
P H
PH
Epstein
C J
CJ
Ferriero
D M
DM
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000098:blood supply / Q000201:enzymology* / Q000473:pathology; D002545:Brain Ischemia / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000235:genetics; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D000860:Hypoxia / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D015227:Lipid Peroxidation / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D018384:Oxidative Stress / Q000235:genetics; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism*
D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase