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Cyclooxygenase-2-dependent neuronal death proceeds via superoxide anion generation

Title
Cyclooxygenase-2-dependent neuronal death proceeds via superoxide anion generation
Authors
Im J.-Y.Kim D.Paik S.-G.Han P.-L.
Ewha Authors
한평림
SCOPUS Author ID
한평림scopus
Issue Date
2006
Journal Title
Free Radical Biology and Medicine
ISSN
0891-5849JCR Link
Citation
vol. 41, no. 6, pp. 960 - 972
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Cyclooxygenase-2 (COX-2) expression is induced in the neurons of the pathologic brain and elevated COX-2 expressions can lead to neuronal death. Here, we report that COX-2 induction in cortical neurons induced by LPS pretreatment for more than 12 h increased the neurotoxic effects of low doses of Fe2+ by more than 2.5-fold. Moreover, the neurotoxicity induced by 30 μM Fe2+ in LPS-pretreated cells exceeded that induced by 100 μM Fe2+ in LPS-untreated cells. LPS pretreatment also similarly aggravated the neurotoxic effects of low doses of H2O2, Zn2+, and sodium nitroprusside. This LPS-induced Fe2+-toxicity enhancement was blocked by trolox, vitamin C, the SOD mimetic MnTBAP, and by the COX-2-specific inhibitor NS398, but not by inhibitors of xanthine oxidase, NADPH oxidase, NOS, and monoamine oxidase. Cortical neurons with enhanced COX-2 expression showed superoxide generation, GSH depletion, and lipid peroxidation in response to low doses of Fe2+, and all of these changes were repressed by MnTBAP or NS398. Consistent with this pharmacological data, cortical neurons prepared from COX-2 knockout mice showed marked reductions in LPS-induced Fe2+-toxicity enhancement and superoxide generation. These results suggest that COX-2 functions as a cellular factor which induces superoxide-mediated cell death in primary cortical neurons. © 2006 Elsevier Inc. All rights reserved.
DOI
10.1016/j.freeradbiomed.2006.06.001
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일반대학원 > 뇌·인지과학과 > Journal papers
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