期刊
NEUROSCIENCE LETTERS
卷 398, 期 3, 页码 230-234出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2006.01.003
关键词
cerebral hemorrhage; ERK MAP kinases; free radicals; iron; oxidative stress; stroke
资金
- NINDS NIH HHS [NS042273] Funding Source: Medline
Hemin is an oxidant that accumulates in intracranial hematomas. Its neurotoxicity is increased by its breakdown, which is catalyzed by the heme oxygenase (HO) enzymes. In this study we tested the hypothesis that inhibiting signaling events mediating HO-1 induction would protect cultured cortical neurons from hemin. A fivefold increase in HO-1 expression was observed in mixed neuron-astrocyte cultures 4 h after hemin exposure. This was markedly reduced by the ERK pathway inhibitor U0126. The JNK inhibitor SP600125 had a weak but statistically significant effect, while the p38 inhibitor SB239063 was ineffective. Hemin neurotoxicity, as assessed by LDH release, propidium iodide staining, and malondialdehyde assay, was also prevented by U0126 but not by SB239063; SP600125 had little or no effect. Consistent with reduced iron release, ferritin expression was also attenuated by U0126, while cell hemin accumulation was increased. These results suggest that targeting the ERK pathway may prevent HO-1 induction in response to hemin, and reduce neuronal injury. (c) 2006 Elsevier Ireland Ltd. All rights reserved.
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