Vitamin E protected cultured cortical neurons from oxidative stress-induced cell death through the activation of mitogen-activated protein kinase and phosphatidylinositol 3-kinase

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 alpha T (alpha-tocopherol), alpha T3 (alpha -tocotrienol), gamma T, and gamma T3 for 24 h prevented the cultured cortical neurons from cell death in oxidative stress stimulated by H2O2, while Trolox, a cell-permeable analog of alpha T, did not. The preventive effect of alpha T was dependent on de novo protein synthesis. Furthermore, we found that alpha T exposure induced the activation of both the MAP kinase (MAPK) and PI3 kinase (PI3K) pathways and that the alpha T-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 alpha T application. The up-regulation of Bcl-2 did not occur in the presence of U0126 or LY294002, suggesting that alpha T-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.