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Activation of NADPH oxidase and extracellular superoxide production in seizure‐induced hippocampal damage
Author(s) -
Patel Manisha,
Li QingYou,
Chang LingYi,
Crapo James,
Liang LiPing
Publication year - 2005
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2004.02838.x
Subject(s) - nadph oxidase , superoxide , kainate receptor , extracellular , hippocampal formation , chemistry , superoxide dismutase , biochemistry , oxidase test , reactive oxygen species , cytosol , biophysics , biology , enzyme , endocrinology , glutamate receptor , receptor , ampa receptor
We sought to determine whether the extracellular compartment contributed to seizure‐induced superoxide (O 2 .− ) production and to determine the role of the NADPH oxidase complex as a source of this O 2 .− production. The translocation of NADPH oxidase subunits (p47 phox , p67 phox and rac1) was assessed by immunoblot analysis and NADPH‐driven O 2 .− production was measured using 2‐(4‐hydroxybenzyl)‐6‐(4‐hydroxyphenyl)‐8‐benzyl‐3,7‐dihydroimidazo [1,2‐α] pyrazin‐3‐one‐enhanced chemiluminescence. Kainate‐induced status epilepticus resulted in a time‐dependent translocation of NADPH oxidase subunits (p47 phox , p67 phox and rac‐1) from hippocampal cytosol to membrane fractions. Hippocampal membrane fractions from kainate‐injected rats showed increased NADPH‐driven and diphenylene iodonium‐sensitive O 2 .− production in comparison to vehicle‐treated rats. The time‐course of kainate‐induced NADPH oxidase activation coincided with microglial activation in the rat hippocampus. Finally, kainate‐induced neuronal damage and membrane oxygen consumption were inhibited in mice overexpressing extracellular superoxide dismutase. These results suggest that seizure activity activates the membrane NADPH oxidase complex resulting in increased formation of O 2 .− .