| First Author | Im JY | Year | 2006 |
| Journal | Free Radic Biol Med | Volume | 41 |
| Issue | 6 | Pages | 960-72 |
| PubMed ID | 16934679 | Mgi Jnum | J:112581 |
| Mgi Id | MGI:3662802 | Doi | 10.1016/j.freeradbiomed.2006.06.001 |
| Citation | Im JY, et al. (2006) Cyclooxygenase-2-dependent neuronal death proceeds via superoxide anion generation. Free Radic Biol Med 41(6):960-72 |
| abstractText | 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 muM Fe2+ in LPS-pretreated cells exceeded that induced by 100 microM 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. |
