An Abnormal Nitric Oxide Metabolism Contributes to Brain Oxidative Stress in the Mouse Model for the Fragile X Syndrome, a Possible Role in Intellectual Disability.

Lima-Cabello, ElenaGarcia-Guirado, FranciscoCalvo-Medina, Rocioel Bekay, RajaaPerez-Costillas, LuciaQuintero-Navarro, CarolinaSanchez-Salido, Lourdesde Diego-Otero, Yolanda2016-09-072016-09-072016Lima-Cabello E, Garcia-Guirado F, Calvo-Medina R, el Bekay R, Perez-Costillas L, Quintero-Navarro C, et al. An Abnormal Nitric Oxide Metabolism Contributes to Brain Oxidative Stress in the Mouse Model for the Fragile X Syndrome, a Possible Role in Intellectual Disability. Oxid Med Cell Longev; 2016:8548910http://hdl.handle.net/10668/2401BACKGROUND: Fragile X syndrome is the most common genetic cause of mental disability. Although many research has been performed, the mechanism underlying the pathogenesis is unclear and needs further investigation. Oxidative stress played major roles in the syndrome. The aim was to investigate the nitric oxide metabolism, protein nitration level, the expression of NOS isoforms, and furthermore the activation of the nuclear factor NF-κB-p65 subunit in different brain areas on the fragile X mouse model. METHODS: This study involved adult male Fmr1-knockout and wild-type mice as controls. We detected nitric oxide metabolism and the activation of the nuclear factor NF-κBp65 subunit, comparing the mRNA expression and protein content of the three NOS isoforms in different brain areas. RESULTS: Fmr1-KO mice showed an abnormal nitric oxide metabolism and increased levels of protein tyrosine nitrosylation. Besides that, nuclear factor NF-κB-p65 and inducible nitric oxide synthase appeared significantly increased in the Fmr1-knockout mice. mRNA and protein levels of the neuronal nitric oxide synthase appeared significantly decreased in the knockout mice. However, the epithelial nitric oxide synthase isoform displayed no significant changes. CONCLUSIONS: These data suggest the potential involvement of an abnormal nitric oxide metabolism in the pathogenesis of the fragile X syndrome.enFragile X syndromeNitric oxide metabolismProtein nitrationNitric oxide synthaseNuclear factor kappa BBrainMouse modelOxidative stressMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Anatomy::Nervous System::Central Nervous System::BrainMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, Animal::Disease Models, AnimalMedical Subject Headings::Diseases::Congenital, Hereditary, and Neonatal Diseases and Abnormalities::Genetic Diseases, Inborn::Genetic Diseases, X-Linked::Mental Retardation, X-Linked::Fragile X SyndromeMedical Subject Headings::Check Tags::MaleMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::MiceMedical Subject Headings::Organisms::Eukaryota::Animals::Animal Population Groups::Animals, Genetically Modified::Mice, Transgenic::Mice, KnockoutMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Transcription Factors::NF-kappa BMedical Subject Headings::Chemicals and Drugs::Inorganic Chemicals::Nitrogen Compounds::Nitrogen Oxides::Nitric OxideMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Oxidoreductases::Oxidoreductases Acting on CH-NH2 Group Donors::Amino Acid Oxidoreductases::Nitric Oxide SynthaseMedical Subject Headings::Phenomena and Processes::Metabolic Phenomena::Metabolism::Oxidative StressMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Protein IsoformsMedical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, MessengerMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Transcription Factors::NF-kappa B::Transcription Factor RelAMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Amino Acids::Amino Acids, Cyclic::Amino Acids, Aromatic::TyrosineAn Abnormal Nitric Oxide Metabolism Contributes to Brain Oxidative Stress in the Mouse Model for the Fragile X Syndrome, a Possible Role in Intellectual Disability.research article26788253open accessAnimalesEncéfaloModelos de enfermedad en animalesSíndrome del cromosoma X frágilMasculinoRatonesRatones noqueadosÓxido nítricoÓxido nítrico sintasaEstrés oxidativoIsoformas de proteínasARN mensajeroFactor de transcripción ReIATirosina10.1155/2016/85489101942-0994PMC4691629