title: Modulation of Brain Glutathione Reductase and Peroxiredoxin 2 by α-Tocopheryl Phosphate.
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.
authors.affiliation: Department of Biochemistry, Federal University of Santa Catarina, 88040-900, Florianopolis, SC, Brazil.
authors.forename: Mariana Figueiroa
authors.initials: MF
authors.lastname: Uchoa
authors.affiliation: Department of Biochemistry, Federal University of Santa Catarina, 88040-900, Florianopolis, SC, Brazil.
authors.forename: Luiz Felipe
authors.initials: LF
authors.lastname: de Souza
authors.affiliation: Department of Biochemistry, Federal University of Santa Catarina, 88040-900, Florianopolis, SC, Brazil.
authors.forename: Danubia Bonfanti
authors.initials: DB
authors.lastname: Dos Santos
authors.affiliation: Department of Biochemistry, Federal University of Santa Catarina, 88040-900, Florianopolis, SC, Brazil.
authors.forename: Tanara Vieira
authors.initials: TV
authors.lastname: Peres
authors.affiliation: Department of Biochemistry, Federal University of Santa Catarina, 88040-900, Florianopolis, SC, Brazil.
authors.forename: Danielle Ferraz
authors.initials: DF
authors.lastname: Mello
authors.affiliation: Department of Biochemistry, Federal University of Santa Catarina, 88040-900, Florianopolis, SC, Brazil.
authors.forename: Rodrigo Bainy
authors.initials: RB
authors.lastname: Leal
authors.affiliation: Department of Biochemistry, Federal University of Santa Catarina, 88040-900, Florianopolis, SC, Brazil.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Farina
authors.affiliation: Department of Biochemistry, Federal University of Santa Catarina, 88040-900, Florianopolis, SC, Brazil. alcir.dafre@ufsc.br.
authors.forename: Alcir Luiz
authors.identifier: http://orcid.org/0000-0001-8097-4611
authors.initials: AL
authors.lastname: Dafre
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000187:drug effects / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism*; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D054464:Peroxiredoxins / Q000378:metabolism*; D024502:alpha-Tocopherol / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000975:Antioxidants; C012552:alpha-tocopherol phosphate; D054464:Peroxiredoxins; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D024502:alpha-Tocopherol
keywords: Antioxidant defense system; Glutathione reductase; Peroxiredoxin; Vitamin E; α-Tocopheryl phosphate