Abstract
Vitamin E family is composed of different tocopherols and tocotrienols that are well-known as antioxidants but that exert also non-antioxidant effects. Oxidative stress may be involved in the progression of neurodegenerative disorders including amyotrophic lateral sclerosis (ALS), characterized by motor neuron death. The aim of the study was the evaluation of the changes induced in the transcriptional profile of NSC-34 motor neurons treated with α-tocopherol. In particular, cells were treated for 24 h with 10 µM α-tocopherol, RNA was extracted and transcriptomic analysis was performed using Next Generation Sequencing. Vitamin E treatment modulated MAPK signaling pathway. The evaluation revealed that 34 and 12 genes, respectively belonging to “Classical MAP kinase pathway” and “JNK and p38 MAP kinase pathway”, were involved. In particular, a downregulation of the genes encoding for p38 (Log2 fold change −0.87 and −0.67) and JNK (Log2 fold change −0.16) was found. On the contrary, the gene encoding for ERK showed a higher expression in cells treated with vitamin E (Log2 fold change 0.30). Since p38 and JNK seem more involved in cell death, while ERK in cell survival, the data suggested that vitamin E treatment may exert a protective role in NSC-34 motor neurons. Moreover, Vitamin E treatment reduced the expression of the genes which encode proteins involved in mitophagy. These results indicate that vitamin E may be an efficacious therapy in preventing motor neuron death, opening new strategies for those diseases that involve motor neurons, including ALS.
Highlights
The vitamin E family includes eight isomers divided into tocopherols and tocotrienols
In order to assess the cytotoxic effects of vitamin E, NSC-34 motor neurons were exposed to different concentrations of vitamin E and the cell viability was evaluated
Since the viability data follow the normal distribution according to Shapiro–Wilk normality test, the statistical analysis was performed using ANOVA and it confirmed no significant variation between control and treated cells (p value > 0.99 for each comparison) (Table 1)
Summary
The vitamin E family includes eight isomers divided into tocopherols and tocotrienols. The antioxidant action of vitamin E is the best known and characterized. The α-tocopherol, that represents the major form of vitamin E in tissues, is well known for its antioxidant action but it is able to exert gene regulation properties [2]. Vitamin E can exert its action through both redox-dependent and independent mechanisms, modulating enzymes and receptors involved in signal transduction and gene expression pathways affecting the action of different transcription factors [3]. The modulation of signal transduction pathways seems to be mediated in a non-antioxidant manner. Vitamin E can modulate pathways involved in Nutrients 2019, 11, 1081; doi:10.3390/nu11051081 www.mdpi.com/journal/nutrients
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