Activation of NADPH oxidase and extracellular superoxide production in seizure‐induced hippocampal damage

Journal of Neurochemistry - Tập 92 Số 1 - Trang 123-131 - 2005
Manisha Patel1, Qing-You Li, Ling‐Yi Chang, James D. Crapo, Li‐Ping Liang
1Department of Pharmaceutical Sciences, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA. [email protected]

Tóm tắt

AbstractWe sought to determine whether the extracellular compartment contributed to seizure‐induced superoxide (O2.−) production and to determine the role of the NADPH oxidase complex as a source of this O2.− production. The translocation of NADPH oxidase subunits (p47phox, p67phox and rac1) was assessed by immunoblot analysis and NADPH‐driven O2.− 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 (p47phox, p67phox and rac‐1) from hippocampal cytosol to membrane fractions. Hippocampal membrane fractions from kainate‐injected rats showed increased NADPH‐driven and diphenylene iodonium‐sensitive O2.− 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 O2.−.

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