Is Vitamin E Toxic to Neuron Cells?

Besides acting as potent free radical scavengers, tocopherols and tocotrienols have been known to have non-antioxidant properties such as the involvement of alpha-tocopherol (alpha T) in PKC pathway and the anti-cancer properties of gamma-tocotrienol (gamma T3). This study aims to elucidate whether protective effects shown by alpha T and gamma T3 in H2O2-induced neuron cultures have anti-apoptotic or pro-apoptotic tendency toward the initiation of neuronal apoptosis. H2O2 is used to induce apoptosis in primary cerebellar neuron cultures which is attenuated by pretreatment of alpha T or gamma T3 at concentrations a parts per thousand currency sign10 mu M. Similar to our previous work, gamma T3 was found to be neurotoxic at concentrations a parts per thousand yen100 mu M, whereas alpha T showed no neurotoxicity. Cellular uptake of gamma T3 was higher than that of alpha T. Treating cells simultaneously with either gamma T3 or alpha T and with then H2O2 led to higher expression of Bax and Bcl-2 than in neurons exposed to H2O2 alone. Analysis of Bcl-2/Bax ratio as 'survival index' showed that both pretreatment of gamma T3 and alpha T followed by H2O2 increase the 'survival index' of Bcl-2/Bax ratio compared to H2O2-treated cells, while treatment of gamma T3 alone decrease the ratio compared to unchanged Bcl2/Bax ratio of similar treatment with alpha T alone. Similar treatment of gamma T3 decreased p53 expression and activates p38 MAPK phosphorylation, whereas alpha T did not alter its expression compared to H2O2-treated cells. Treating neurons with only gamma T3 or alpha T increased the expression of Bax, Bcl-2, p53, and p38 MAPK compared to control with gamma T3 exerting stronger expression for proteins involved than alpha T. In conclusion, low doses of gamma T3 and alpha T confer neuroprotection to H2O2-treated neurons via their antioxidant mechanism but gamma T3 has stronger pro-apoptosis tendency than alpha T by activating molecules involved in the neuronal apoptotic pathway in the absence of H2O2.