Vitamin E Protected Cultured Cortical Neurons from Oxidative Stress-induced Cell Death Through the Activation of Mitogen-activated Protein Kinase and Phosphatidylinositol 3-kinase.
From: Human Stress Signal Research Center, National Institute of Advanced Industrial Science and Technology (AIST), Midorigaoka, Ikeda, Osaka, Japan. numakawa@ncnp.go.jp
Journal of neurochemistry
- Publish Date: May 2006
- ISSN: 0022-3042
- Volume: 97
- Issue: 4
- Pages: 1191-202
- Medium: Print
- Language: English
- Citation (JAMA): Numakawa Yumiko, Numakawa Tadahiro, Matsumoto Tomoya, et al. Vitamin E Protected Cultured Cortical Neurons from Oxidative Stress-induced Cell Death Through the Activation of Mitogen-activated Protein Kinase and Phosphatidylinositol 3-kinase.. J. Neurochem. May 2006;97:1191-202
Abstract
The role of vitamin E in the CNS has not been fully elucidated. In the present study, we found that pre-treatment with vitamin E analogs including alphaT (alpha-tocopherol), alphaT3 (alpha -tocotrienol), gammaT, and gammaT3 for 24 h prevented the cultured cortical neurons from cell death in oxidative stress stimulated by H2O2, while Trolox, a cell-permeable analog of alphaT, did not. The preventive effect of alphaT was dependent on de novo protein synthesis. Furthermore, we found that alphaT exposure induced the activation of both the MAP kinase (MAPK) and PI3 kinase (PI3K) pathways and that the alphaT-dependent survival effect was blocked by the inhibitors, U0126 (an MAPK pathway inhibitor) or LY294002 (a PI3K pathway inhibitor). Interestingly, the up-regulation of Bcl-2 (survival promoting molecule) was induced by alphaT application. The up-regulation of Bcl-2 did not occur in the presence of U0126 or LY294002, suggesting that alphaT-up-regulated Bcl-2 is mediated by these kinase pathways. These observations suggest that vitamin E analogs play an essential role in neuronal maintenance and survival in the CNS.
Mesh Headings (Keywords): 1-Phosphatidylinositol 3-Kinase, Animals, Animals, Newborn, Cell Death, Cell Survival, Cells, Cultured, Cerebral Cortex, Chromans, Cytoprotection, Enzyme Inhibitors, MAP Kinase Signaling System, Mitogen-Activated Protein Kinase 1, Neurons, Neuroprotective Agents, Oxidative Stress, Proto-Oncogene Proteins c-bcl-2, Rats, Up-Regulation, Vitamin E, alpha-Tocopherol
Check for Full Text / PubMed Unique Identifier (PMID): 16686696
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