Impaired PLP-dependent metabolism in brain samples from Huntington disease patients and transgenic R6/1 mice

Sorolla Bardají, Maria Alba; Rodríguez Colman, Maria José; Vall-llaura Espinosa, Núria; Vived Maza, Celia; Fernández Nogales, Marta; Lucas, José J.; Ferrer, Isidre; Cabiscol Català, Elisa

doi:https://doi.org/10.1007/s11011-015-9777-7

View/Open

023606.pdf (755.1Kb)
Sol·licita una còpia

Issue date

2016-06

Author

Sorolla Bardají, Maria Alba

Rodríguez Colman, Maria José

Vall-llaura Espinosa, Núria

Vived Maza, Celia

Fernández Nogales, Marta

Lucas, José J.

Ferrer, Isidre

Cabiscol Català, Elisa

Suggested citation

Sorolla Bardají, Maria Alba; Rodríguez Colman, Maria José; Vall-llaura Espinosa, Núria; Vived Maza, Celia; Fernández Nogales, Marta; Lucas, José J.; ... Cabiscol Català, Elisa. (2016) . Impaired PLP-dependent metabolism in brain samples from Huntington disease patients and transgenic R6/1 mice. Metabolic Brain Disease, 2016, vol. 31, num. 3, p. 579-586. https://doi.org/10.1007/s11011-015-9777-7.

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 5A '-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.

URI

http://hdl.handle.net/10459.1/57916

DOI

https://doi.org/10.1007/s11011-015-9777-7

Is part of

Metabolic Brain Disease, 2016, vol. 31, num. 3, p. 579-586