Alpha-tocopherol at nanomolar concentrations increases the viability of PC12 cells under oxidative stress conditions. The effects of modulation of signaling systems

We found that long-term preincubation of neuronal-like PC12 cells with α-tocopherol at micro- as well as nanomolar concentrations significantly increased cell viability under oxidative stress conditions. We discovered that the protective effect of α-tocopherol increases with an increase in its concentration in the 1–100 nM range, while its effects at concentrations of 100 nM, 1, 10, and 100 μM were similar when α-tocopherol was applied to cells 12–18 h prior to H2O2. An important role in the protective effect of long-term pre-incubation of cells with α-tocopherol at various concentrations is probably related to its modulatory influence on the activities of protein kinase C, extracellular signal-activated protein kinase, and phosphatidylinositol 3-kinase. Short-term preincubation of PC12 cells with this antioxidant at nanomolar concentrations for 0.5 or 1.5 h practically did not influence cell viability, while the protective effect of α-tocopherol at micromolar concentrations was probably related to its ability to terminate free-radical reactions due to direct interactions with free radicals.