Abstract
Besides acting as potent free radical scavengers, tocopherols and tocotrienols have been known to have non-antioxidant properties such as the involvement of α-tocopherol (αT) in PKC pathway and the anti-cancer properties of γ-tocotrienol (γT3). This study aims to elucidate whether protective effects shown by αT and γT3 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 αT or γT3 at concentrations ≤10 μM. Similar to our previous work, γT3 was found to be neurotoxic at concentrations ≥100 μM, whereas αT showed no neurotoxicity. Cellular uptake of γT3 was higher than that of αT. Treating cells simultaneously with either γT3 or αT 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 γT3 and αT followed by H2O2 increase the ‘survival index’ of Bcl-2/Bax ratio compared to H2O2-treated cells, while treatment of γT3 alone decrease the ratio compared to unchanged Bcl2/Bax ratio of similar treatment with αT alone. Similar treatment of γT3 decreased p53 expression and activates p38 MAPK phosphorylation, whereas αT did not alter its expression compared to H2O2-treated cells. Treating neurons with only γT3 or αT increased the expression of Bax, Bcl-2, p53, and p38 MAPK compared to control with γT3 exerting stronger expression for proteins involved than αT. In conclusion, low doses of γT3 and αT confer neuroprotection to H2O2-treated neurons via their antioxidant mechanism but γT3 has stronger pro-apoptosis tendency than αT by activating molecules involved in the neuronal apoptotic pathway in the absence of H2O2.
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Acknowledgments
This study was funded by the Ministry of Science, Technology, and Innovation of Malaysia under Intensified Research Prioritized Area (IRPA) grant 06-02-02-0022/PR0008/09-07. We thank Dr. Coral Sanfeliu from the Institute of Biomedical Research of Barcelona (IIBB) in Spain for her invaluable assistance in setting of the neuronal culture system in our laboratory.
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Then, S.M., Mazlan, M., Mat Top, G. et al. Is Vitamin E Toxic to Neuron Cells?. Cell Mol Neurobiol 29, 485–496 (2009). https://doi.org/10.1007/s10571-008-9340-8
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DOI: https://doi.org/10.1007/s10571-008-9340-8