Charlotte Veyrat-Durebex1,2, Christelle Debeissat3,4, Hélène Blasco5,6, Franck Patin5,6, Hélène Henique7,8, Patrick Emond6, Catherine Antar5,6, Valérie Gissot9, Olivier Herault3,4, François Maillot7,8. 1. Laboratoire de biochimie et biologie moléculaire, hôpital Bretonneau CHRU de Tours, Tours, France. charlotte.veyrat@live.fr. 2. INSERM U930, Université François Rabelais Tours, Tours, France. charlotte.veyrat@live.fr. 3. CNRS UMR 7292 - équipe LNOx, Université François Rabelais Tours, Tours, France. 4. Service d'hématologie biologique, CHRU de Tours, Tours, France. 5. Laboratoire de biochimie et biologie moléculaire, hôpital Bretonneau CHRU de Tours, Tours, France. 6. INSERM U930, Université François Rabelais Tours, Tours, France. 7. Service de médecine interne, CHRU de Tours, Tours, France. 8. INSERM U1069, Université François Rabelais Tours, Tours, France. 9. INSERM CIC 1415, CHRU de Tours, Tours, France.
Abstract
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.
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 PKUpatients 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 PKUpatients 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 PKUpatients 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.
Entities:
Keywords:
PKU; Phenylketonuria; RNA antioxidant profile; Redox status
Authors: Danique van Vliet; Vibeke M Bruinenberg; Priscila N Mazzola; Martijn Hjr van Faassen; Pim de Blaauw; Tiziana Pascucci; Stefano Puglisi-Allegra; Ido P Kema; M Rebecca Heiner-Fokkema; Eddy A van der Zee; Francjan J van Spronsen Journal: Am J Clin Nutr Date: 2016-09-21 Impact factor: 7.045
Authors: C Sierra; M A Vilaseca; D Moyano; N Brandi; J Campistol; N Lambruschini; F J Cambra; R Deulofeu; A Mira Journal: Clin Chim Acta Date: 1998-08-10 Impact factor: 3.786