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Nutrition & Metabolism
Published in: Nutrition & Metabolism 1/2012

Open Access 01-12-2012 | Research

γ-Tocotrienol does not substantially protect DS neurons from hydrogen peroxide-induced oxidative injury

Authors: Sue-Mian Then, Coral Sanfeliu, Gapor M Top, Wan Zurinah Wan Ngah, Musalmah Mazlan

Published in: Nutrition & Metabolism | Issue 1/2012

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Abstract

Background

Down syndrome (DS) neurons are more susceptible to oxidative stress and previous studies have shown that vitamin E was able to reduce oxidative stress and improve DS neurons' viability. Therefore, this study was done to investigate the protective role of γ-tocotrienol (γT3) in DS neurons from hydrogen peroxide (H2O2) -induced oxidative stress. The pro-apoptosis tendency of γT3 was compared to α-tocopherol (αT) in non-stress condition as well.

Methods

Primary culture of DS and euploid neurons were divided into six groups of treatment: control, H2O2, γT3 pre-treatment with H2O2, γT3 only, αT pre-treatment with H2O2 and αT only. The treatments were assessed by MTS assay and apoptosis assay by single-stranded DNA (ssDNA) apoptosis ELISA assay, Hoechst and Neu-N immunofluorescence staining. The cellular uptake of γT3 and αT was determined by HPLC while protein expressions were determined by Western blot. Comparison between groups was made by the Student's t test, one-way ANOVA and Bonferroni adjustment as well as two-way ANOVA for multiple comparisons.

Results

One day incubation of γT3 was able to reduced apoptosis of DS neurons by 10%, however γT3 was cytotoxic at longer incubation period (14 days) and at concentrations ≥ 100 μM. Pre-treatment of αT and γT3 only attenuate apoptosis and increase cell viability in H2O2-treated DS and euploid neurons by 10% in which the effects were minimal to maintain most of the DS cells' morphology. γT3 act as a free radical scavenger by reducing ROS generated by H2O2. In untreated controls, DS neurons showed lower Bcl-2/Bax ratio and p53 expression compared to normal neurons, while cPKC and PKC-δ expressions were higher in DS neurons. On the other hand, pre-treatment of γT3 in H2O2-treated DS neurons have reduced Bcl-2/Bax ratio, which was not shown in euploid neurons. This suggests that pre-treatment of γT3 did not promote DS cell survival. Meanwhile γT3 and αT treatments without H2O2 as well as pre-treatment of γT3 and αT induced changes in cPKC and PKC-δ expression in DS neurons suggesting interaction of γT3 and αT with PKC activity.

Conclusion

Our study suggests that γT3 pre-treatment are not sufficient to protect DS neurons from H2O2-induced oxidative assault, instead induced the apoptosis process.
Appendix
Available only for authorised users
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Metadata
Title
γ-Tocotrienol does not substantially protect DS neurons from hydrogen peroxide-induced oxidative injury
Authors
Sue-Mian Then
Coral Sanfeliu
Gapor M Top
Wan Zurinah Wan Ngah
Musalmah Mazlan
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Nutrition & Metabolism / Issue 1/2012
Electronic ISSN: 1743-7075
DOI
https://doi.org/10.1186/1743-7075-9-1

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