Protein oxidation in Huntington disease affects energy production and vitamin B6 metabolism
Issue date
2010Author
Ortega, Zaira
Lucas, José J.
Ferrer, Isidre
Suggested citation
Sorolla Bardají, Maria Alba;
Rodríguez Colman, Maria José;
Tamarit Sumalla, Jordi;
Ortega, Zaira;
Lucas, José J.;
Ferrer, Isidre;
...
Cabiscol Català, Elisa.
(2010)
.
Protein oxidation in Huntington disease affects energy production and vitamin B6 metabolism.
Free Radical Biology and Medicine, 2010, vol. 49, núm. 4, p. 612-621.
https://doi.org/10.1016/j.freeradbiomed.2010.05.016.
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Show full item recordAbstract
Huntington disease (HD) is an inherited neurodegenerative disorder that initially affects the striatum and
progressively the cortex. Oxidative stress in HD has been described as important to disease progression. In this
study, protein carbonylation, used as a marker of protein oxidation, was analyzed in human brain striatum. A
comparison of HD samples tomatched controls identified 13 carbonylated proteins, including enzymes involved
in the glycolytic pathway and mitochondrial proteins related to ATP production. Oxidation of the mitochondrial
enzymes resulted in decreased catalytic activity, in good agreement with the energy deficiency observed in HD.
Wealso found carbonylation of pyridoxal kinase and antiquitin 1, both involved in themetabolismof pyridoxal 5-
phosphate, the active formof vitamin B6. The Tet/HD94 conditionalmousemodel allowed us to demonstrate that
increased carbonylation in striatum is dependent on mutant huntingtin expression. As in humans, pyridoxal
kinase showed decreased levels and was highly carbonylated in the gene-on mice; these modifications were
reverted in the gene-offmice. Wehypothesize that both pyridoxal kinase and antiquitin 1 oxidation could result
in decreased pyridoxal 5-phosphate availability necessary as a cofactor in transaminations, synthesis of
glutathione, and synthesis of GABA and dopamine, two neurotransmitters that play a key role in HD pathology.