Alpha-Tocopherol at Nanomolar Concentrations Increases the Viability of PC 12 Cells under Gxidative Stress Conditions. The Effects of Modulation of Signaling Systems

摘要

We found that long-term preincubation of neuronal-like PC 12 cells with a-tocopherol at micro-as well as nanomolar concentrations significantly increased cell viability under oxidative stress conditions. We discovered that the protective effect of a-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 muM were similar when a-tocopherol was applied to cells 12- 18 h prior to H_2O_2. An important role in the protective effect of long-term preincubation of cells with a-tocopherol at various concentrations is probably related to its modulatory influence on the activities of protein kinase C, extracellular signal-activated protein kinase, and phosphatidylinos-itol 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 a-tocopherol at micro-molar concentrations was probably related to its ability to terminate free-radical reactions due to direct interactions with free radicals.