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Vitamin E protected cultured cortical neurons from oxidative stress‐induced cell death through the activation of mitogen‐activated protein kinase and phosphatidylinositol 3‐kinase
Author(s) -
Numakawa Yumiko,
Numakawa Tadahiro,
Matsumoto Tomoya,
Yagasaki Yuki,
Kumamaru Emi,
Kunugi Hiroshi,
Taguchi Takahisa,
Niki Etsuo
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.03827.x
Subject(s) - ly294002 , mapk/erk pathway , kinase , oxidative stress , programmed cell death , protein kinase a , microbiology and biotechnology , pi3k/akt/mtor pathway , trolox , phosphatidylinositol , ask1 , biology , mitogen activated protein kinase , chemistry , signal transduction , mitogen activated protein kinase kinase , biochemistry , apoptosis , antioxidant capacity
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 αT (α‐tocopherol), αT3 (α ‐tocotrienol), γT, and γT3 for 24 h prevented the cultured cortical neurons from cell death in oxidative stress stimulated by H 2 O 2 , while Trolox, a cell‐permeable analog of αT, did not. The preventive effect of αT was dependent on de novo protein synthesis. Furthermore, we found that αT exposure induced the activation of both the MAP kinase (MAPK) and PI3 kinase (PI3K) pathways and that the αT‐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 αT application. The up‐regulation of Bcl‐2 did not occur in the presence of U0126 or LY294002, suggesting that αT‐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.