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Simvastatin prevents oxygen and glucose deprivation/reoxygenation-induced death of cortical neurons by reducing the production and toxicity of 4-hydroxy-2E-nonenal

Title
Simvastatin prevents oxygen and glucose deprivation/reoxygenation-induced death of cortical neurons by reducing the production and toxicity of 4-hydroxy-2E-nonenal
Authors
Lim J.H.Lee J.-C.Lee Y.H.Choi I.Y.Oh Y.-K.Kim H.-S.Park J.-S.Kim W.-K.
Ewha Authors
김원기김희선
SCOPUS Author ID
김희선scopus
Issue Date
2006
Journal Title
Journal of Neurochemistry
ISSN
0022-3042JCR Link
Citation
vol. 97, no. 1, pp. 140 - 150
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Lipid membrane peroxidation is highly associated with neuronal death in various neurodegenerative diseases including cerebral stroke. Here, we report that simvastatin decreases oxygen and glucose deprivation (OGD)/reoxygenation- evoked neuronal death by inhibiting the production and cytoxicity of 4-hydroxy-2E-nonenal (HNE), the final product of lipid peroxidation. Simvastatin markedly decreased the OGD/reoxygenation-evoked death of cortical neurons. OGD/reoxygenation increased the intracellular HNE level mostly in neuronal cells, not glial cells. Simvastatin decreased the intracellular level of HNE in neuronal cells exposed to OGD/reoxygenation. We further found that HNE induced the cytotoxicity in neuronal cells and synergistically increased the N-methyl-D-aspartate (NMDA) receptor-mediated excitotoxicity. Simvastatin largely blocked the NMDA neurotoxicity potentiated by HNE. However, simvastatin did not alter the NMDA-evoked calcium influx in the absence or presence of HNE. HNE inhibited the activity of nuclear factor-kappa B (NF-κB), and the cytotoxicity of HNE was in good correlation with inactivation of NF-κB. Simvastatin reversed the inhibition of NF-κB activity induced by OGD/reoxygenation or HNE. The neuroprotection by simvastatin was significantly attenuated by various NF-κB inhibitors, implying that simvastatin inhibits the cytotoxicity of HNE at least in part by maintaining the activity of NF-κB. Further understanding of the neuroprotective mechanism of simvastatin may provide a therapeutic strategy for oxidative stress-related neurodegenerative diseases. © 2006 The Authors.
DOI
10.1111/j.1471-4159.2006.03715.x
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자연과학대학 > 화학·나노과학전공 > Journal papers
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