Protein oxidation in Huntington disease affects energy production and vitamin B6 metabolism

Free Radical Biology & Medicine
M Alba SorollaE Cabiscol

Abstract

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 to matched 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. We also found carbonylation of pyridoxal kinase and antiquitin 1, both involved in the metabolism of pyridoxal 5-phosphate, the active form of vitamin B6. The Tet/HD94 conditional mouse model 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-off mice. We hypothesize that both pyridoxal kinase and antiquitin 1 oxidation could result in decreased pyridoxal 5-phosphate avail...Continue Reading

Citations

Sep 5, 2013·International Journal of Molecular Sciences·Krishnan VenkataramanT C Tai
Jan 22, 2013·Journal of Proteomics·Annika HöhnTilman Grune
Dec 18, 2013·Pharmacology & Therapeutics·Juliana Navarro-YepesRodrigo Franco
Jan 19, 2011·Journal of Proteomics·Angelo D'AlessandroLello Zolla
Apr 24, 2015·Biomolecules·Mark RinnerthalerKlaus Richter
May 15, 2012·Journal of Proteomics·Jordi TamaritJoaquim Ros
Dec 28, 2010·Chemico-biological Interactions·Chi-Lung ChanWing-Ping Fong
Jun 19, 2014·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Lydie BoussicaultGilles Bonvento
Jul 27, 2015·Clinical Biochemistry·Marisol Peña-SánchezSergio González-García
Apr 5, 2012·BioFactors·M Alba SorollaElisa Cabiscol
Apr 11, 2014·Journal of Neurochemistry·Michelle Muller, Blair R Leavitt
Jun 17, 2014·Mass Spectrometry Reviews·D Allan ButterfieldRenã A S Robinson
Aug 16, 2014·Movement Disorders : Official Journal of the Movement Disorder Society·Wenzhen DuanJing Jin
Oct 12, 2013·Mass Spectrometry Reviews·Elisa CabiscolJoaquim Ros
Jan 3, 2014·Biochimica Et Biophysica Acta·Li Gan, Jeffrey A Johnson
Dec 6, 2011·Biochimica Et Biophysica Acta·Ashu Johri, M Flint Beal
Sep 13, 2013·Toxicology Mechanisms and Methods·Xiuzhen FanM Firoze Khan
Apr 23, 2013·Free Radical Biology & Medicine·Sylvette Ayala-Peña
Apr 23, 2013·Free Radical Biology & Medicine·Ashu JohriM Flint Beal
Oct 23, 2013·Free Radical Biology & Medicine·Elie HatemStéphane Chédin
Sep 15, 2012·Neurobiology of Disease·Ilenia VenturaMargherita Bignami
Sep 24, 2016·Journal of Huntington's Disease·Amit Kumar, Rajiv R Ratan
Nov 11, 2017·Journal of Huntington's Disease·Janet M Dubinsky
Jun 6, 2020·Antioxidants & Redox Signaling·Lígia Fão, Ana Cristina Rego
Jan 12, 2019·Neurotoxicity Research·Musthafa Mohamed EssaMohammed Akbar
Feb 26, 2020·Autophagy·Sandra Franco-IborraMarta Martinez-Vicente
Sep 13, 2012·Experimental and Therapeutic Medicine·Ling YuYuan-Qing Yao
Oct 5, 2018·Frontiers in Molecular Neuroscience·Ju ZhengBeidong Liu
Feb 4, 2021·Neurochemistry International·Yuyu NanQinghua Li
Oct 28, 2019·Journal of Proteome Research·Atef Mannaa, Franz-Georg Hanisch
Apr 26, 2011·Archives of Biochemistry and Biophysics·M Alba SorollaElisa Cabiscol

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