α-Tocopherol is a lipophilic vitamin that exhibits an antioxidative activity. The purpose of this study was to clarify the roles of α-tocopherol in the regulation of intracellular glutathione (GSH) levels in HaCaT keratinocytes. When HaCaT keratinocytes were cultivated with α-tocopherol for 24h, the intracellular GSH was increased at every concentration of α-tocopherol tested. Furthermore, the HaCaT keratinocytes cultured with α-tocopherol at 50 μM for 24h exhibited resistance against H2O2. However, a short exposure of HaCaT keratinocytes to α-tocopherol for 1 h did not influence either the GSH level or the resistance to H2O2. These findings suggest that GSH, which is inductively synthesized by α-tocopherol, effectively reduces exogenous oxidative stress. To evaluate the effect of α-tocopherol on the GSH level, BSO, which is a typical inhibitor of γ-glutamylcysteine synthetase (γ-GCS), was used. When BSO was added to HaCaT keratinocytes, no action of α-tocopherol on the GSH level was observed. On the other hand, α-tocopherol resulted in the up-regulation of γ-GCS-HS (heavy subunit) mRNA. In addition, water soluble α-tocopherol derivatives (α-tocopherol phosphate and trolox) caused no changes in GSH level. From these results, it was concluded that α-tocopherol increases the intracellular GSH level of HaCaT keratinocytes through the up-regulation of γ-GCS-HS mRNA.
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