Hyperphenylalaninemia Correlated with Global Decrease of Antioxidant Genes Expression in White Blood Cells of Adult Patients with Phenylketonuria.

Autor:	Veyrat-Durebex C; Laboratoire de biochimie et biologie moléculaire, hôpital Bretonneau CHRU de Tours, Tours, France. charlotte.veyrat@live.fr.; INSERM U930, Université François Rabelais Tours, Tours, France. charlotte.veyrat@live.fr., Debeissat C; CNRS UMR 7292 - équipe LNOx, Université François Rabelais Tours, Tours, France.; Service d'hématologie biologique, CHRU de Tours, Tours, France., Blasco H; Laboratoire de biochimie et biologie moléculaire, hôpital Bretonneau CHRU de Tours, Tours, France.; INSERM U930, Université François Rabelais Tours, Tours, France., Patin F; Laboratoire de biochimie et biologie moléculaire, hôpital Bretonneau CHRU de Tours, Tours, France.; INSERM U930, Université François Rabelais Tours, Tours, France., Henique H; Service de médecine interne, CHRU de Tours, Tours, France.; INSERM U1069, Université François Rabelais Tours, Tours, France., Emond P; INSERM U930, Université François Rabelais Tours, Tours, France., Antar C; Laboratoire de biochimie et biologie moléculaire, hôpital Bretonneau CHRU de Tours, Tours, France.; INSERM U930, Université François Rabelais Tours, Tours, France., Gissot V; INSERM CIC 1415, CHRU de Tours, Tours, France., Herault O; CNRS UMR 7292 - équipe LNOx, Université François Rabelais Tours, Tours, France.; Service d'hématologie biologique, CHRU de Tours, Tours, France., Maillot F; Service de médecine interne, CHRU de Tours, Tours, France.; INSERM U1069, Université François Rabelais Tours, Tours, France.
Jazyk:	angličtina
Zdroj:	JIMD reports [JIMD Rep] 2017; Vol. 37, pp. 73-83. Date of Electronic Publication: 2017 Mar 15.
DOI:	10.1007/8904_2017_16
Abstrakt:	Background: Several studies have highlighted disturbance of redox homeostasis in patients with phenylketonuria (PKU) which may be associated with neurological disorders observed in patients, especially during adulthood when phenylalanine restrictive diets are not maintained. The aim of this study was to assess the antioxidant profile in a cohort of PKU patients in comparison to the controls and to evaluate its relation to biochemical parameters especially phenylalaninemia. Methods: We measured RNA expression of 22 antioxidant genes and reactive oxygen species (ROS) levels in white blood cells of 10 PKU patients and 10 age- and gender-matched controls. We also assessed plasma amino acids, vitamins, oligo-elements, and urinary organic acids concentrations. Then we evaluated the relationship between redox status and biochemical parameters. Results: In addition to expected biochemical disturbances, we highlighted a significant global decrease of antioxidant genes expression in PKU patients in comparison to the controls. This global decrease of antioxidant genes expression, including various isoforms of peroxiredoxins, glutaredoxins, glutathione peroxidases, and superoxide dismutases, was significantly correlated to hyperphenylalaninemia. Conclusion: This study is the first to evaluate the expression of 22 antioxidant genes in white blood cells regarding biochemical parameters in PKU. These findings highlight the association of hyperphenylalaninemia with antioxidant genes expression. New experiments to specify the role of oxidative stress in PKU pathogenesis may be useful in suggesting new recommendations in PKU management and new therapeutic trials based on antioxidant defenses.
Databáze:	MEDLINE
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