Abstract
α-Tocopheryl phosphate (αTP) is a phosphorylated form of α-tocopherol. Since it is phosphorylated in the hydroxyl group that is essential for the antioxidant property of α-tocopherol, we hypothesized that αTP would modulate the antioxidant system, rather than being an antioxidant agent per se. α-TP demonstrated antioxidant activity in vitro against iron-induced oxidative stress in a mitochondria-enriched fraction preparation treated with 30 or 100 µM α-TP. However, this effect was not observed ex vivo with mitochondrial-enriched fraction from mice treated with an intracerebroventricular injection of 0.1 or 1 nmol/site of αTP. Two days after treatment (1 nmol/site αTP), peroxiredoxin 2 (Prx2) and glutathione reductase (GR) expression and GR activity were decreased in cerebral cortex and hippocampus. Glutathione content, glutathione peroxidase, and thioredoxin reductase activities were not affected by αTP. In conclusion, the persistent decrease in GR and Prx2 protein content is the first report of an in vivo effect of αTP on protein expression in the mouse brain, potentially associated to a novel and biologically relevant function of this naturally occurring compound.
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Acknowledgments
This work was supported by the Santa Catarina State Research Fundation (FAPESC #1348/2010-0), the National Council for Research and Development (CNPq #481488/2012-0), and Network Brazilian Institute of Neuroscience (IBN-Net # 01.06.0842-00). Scholarships were provided by the Coordination for the Improvement of Higher Level Education (CAPES) to Danubia B. do Santos, and Tanara V. Peres, and by CNPq to Mariana F. Uchoa and Luiz Felipe de Souza. Alcir L. Dafre, Marcelo Farina and Rodrigo Bainy Leal are CNPq research productivity fellows. We would like to thank Luciane Perazzolo, Andiara Espíndola de Freitas and Ana Lucia Severo Rodrigues from the Federal University of Santa Catarina for helping with some experiments.
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Uchoa, M.F., de Souza, L.F., dos Santos, D.B. et al. Modulation of Brain Glutathione Reductase and Peroxiredoxin 2 by α-Tocopheryl Phosphate. Cell Mol Neurobiol 36, 1015–1022 (2016). https://doi.org/10.1007/s10571-015-0298-z
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DOI: https://doi.org/10.1007/s10571-015-0298-z