title: Antioxidants successfully reduce ROS production in propionic acidemia fibroblasts.
abstract: Propionic acidemia (PA), caused by a deficiency of the mitochondrial biotin dependent enzyme propionyl-CoA carboxylase (PCC) is one of the most frequent organic acidurias in humans. Most PA patients present in the neonatal period with metabolic acidosis and hyperammonemia, developing different neurological symptoms, movement disorders and cardiac complications. There is strong evidence indicating that oxidative damage could be a pathogenic factor in neurodegenerative, mitochondrial and metabolic diseases. Recently, we identified an increase in ROS levels in PA patients-derived fibroblasts. Here, we analyze the capability of seven antioxidants to scavenge ROS production in PA patients' cells. Tiron, trolox, resveratrol and MitoQ significantly reduced ROS content in patients and controls' fibroblasts. In addition, changes in the expression of two antioxidant enzymes, superoxide dismutase and glutathione peroxidase, were observed in PA patients-derived fibroblasts after tiron and resveratrol treatment. Our results in PA cellular models establish the proof of concept of the potential of antioxidants as an adjuvant therapy for PA and pave the way for future assessment of antioxidant strategies in the murine model of PA.
authors.affiliation: Centro de Biología Molecular "Severo Ochoa", UAM-CSIC, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), IdiPAZ, Madrid, Spain.
authors.forename: Lorena
authors.initials: L
authors.lastname: Gallego-Villar
authors.affiliation: Centro de Biología Molecular "Severo Ochoa", UAM-CSIC, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), IdiPAZ, Madrid, Spain.
authors.forename: Belén
authors.initials: B
authors.lastname: Pérez
authors.affiliation: Centro de Biología Molecular "Severo Ochoa", UAM-CSIC, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), IdiPAZ, Madrid, Spain.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Ugarte
authors.affiliation: Centro de Biología Molecular "Severo Ochoa", UAM-CSIC, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), IdiPAZ, Madrid, Spain.
authors.forename: Lourdes R
authors.initials: LR
authors.lastname: Desviat
authors.affiliation: Centro de Biología Molecular "Severo Ochoa", UAM-CSIC, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), IdiPAZ, Madrid, Spain. Electronic address: erichard@cbm.csic.es.
authors.forename: Eva
authors.initials: E
authors.lastname: Richard
mesh_terms: D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D002839:Chromans / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression / Q000187:drug effects; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D043586:Methylmalonyl-CoA Decarboxylase / Q000235:genetics; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009154:Mutation; D009943:Organophosphorus Compounds / Q000494:pharmacology; D061251:Primary Cell Culture; D056693:Propionic Acidemia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D014451:Ubiquinone / Q000031:analogs & derivatives / Q000494:pharmacology; D000094765:Glutathione Peroxidase GPX1
chemical_list: D000975:Antioxidants; D002839:Chromans; D009943:Organophosphorus Compounds; D017382:Reactive Oxygen Species; D013267:Stilbenes; D014451:Ubiquinone; C429014:mitoquinone; D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D043586:Methylmalonyl-CoA Decarboxylase; D000077185:Resveratrol; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human
keywords: Antioxidants; MitoQ; Propionic acidemia; Resveratrol; Tiron; Trolox