title: Impaired PLP-dependent metabolism in brain samples from Huntington disease patients and transgenic R6/1 mice.
abstract: Oxidative stress has been described as important to Huntington disease (HD) progression. In a previous HD study, we identified several carbonylated proteins, including pyridoxal kinase and antiquitin, both of which are involved in the metabolism of pyridoxal 5´-phosphate (PLP), the active form of vitamin B6. In the present study, pyridoxal kinase levels were quantified and showed to be decreased both in HD patients and a R6/1 mouse model, compared to control samples. A metabolomic analysis was used to analyze metabolites in brain samples of HD patients and R6/1 mice, compared to control samples using mass spectrometry. This technique allowed detection of increased concentrations of pyridoxal, the substrate of pyridoxal kinase. In addition, PLP, the product of the reaction, was decreased in striatum from R6/1 mice. Furthermore, glutamate and cystathionine, both substrates of PLP-dependent enzymes were increased in HD. This reinforces the hypothesis that PLP synthesis is impaired, and could explain some alterations observed in the disease. Together, these results identify PLP as a potential therapeutic agent.
authors.affiliation: Departament de Ciències Mèdiques Bàsiques, Universitat de Lleida, IRBLleida, Av. Rovira Roure 80, 25198, Lleida, Catalonia, Spain. alba.sorolla@cmb.udl.cat.
authors.forename: M Alba
authors.initials: MA
authors.lastname: Sorolla
authors.affiliation: Departament de Ciències Mèdiques Bàsiques, Universitat de Lleida, IRBLleida, Av. Rovira Roure 80, 25198, Lleida, Catalonia, Spain.
authors.forename: María José
authors.initials: MJ
authors.lastname: Rodríguez-Colman
authors.affiliation: Departament de Ciències Mèdiques Bàsiques, Universitat de Lleida, IRBLleida, Av. Rovira Roure 80, 25198, Lleida, Catalonia, Spain.
authors.forename: Núria
authors.initials: N
authors.lastname: Vall-Llaura
authors.affiliation: Departament de Ciències Mèdiques Bàsiques, Universitat de Lleida, IRBLleida, Av. Rovira Roure 80, 25198, Lleida, Catalonia, Spain.
authors.forename: Celia
authors.initials: C
authors.lastname: Vived
authors.affiliation: Centro de Biología Molecular "Severo Ochoa", Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Fernández-Nogales
authors.affiliation: Centro de Biología Molecular "Severo Ochoa", Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: José J
authors.initials: JJ
authors.lastname: Lucas
authors.affiliation: Institut de Neuropatologia, Servei Anatomia Patològica, IDIBELL-Hospital Universitari de Bellvitge, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Isidre
authors.initials: I
authors.lastname: Ferrer
authors.affiliation: Departament de Ciències Mèdiques Bàsiques, Universitat de Lleida, IRBLleida, Av. Rovira Roure 80, 25198, Lleida, Catalonia, Spain.
authors.forename: Elisa
authors.initials: E
authors.lastname: Cabiscol
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism*; D003540:Cystathionine / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D006816:Huntington Disease / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology*; D011732:Pyridoxal Phosphate / Q000378:metabolism*; D055815:Young Adult
chemical_list: D003540:Cystathionine; D018698:Glutamic Acid; D011732:Pyridoxal Phosphate
keywords: Cystathionine; Glutamate; Huntington disease; Oxidative stress; Pyridoxal 5-phosphate; Pyridoxal kinase