Increased glucose metabolism and atp level in brain tissue of Huntington's disease transgenic mice.

J. Olah, P. Kliveny, G. Gardian, L. Vecsey, F. Orosz, G.G. Kovacs, H.V. Westerhoff, J. Ovadi

    Research output: Contribution to JournalArticleAcademicpeer-review

    Abstract

    Huntington's disease (HD) is a progressive neurodegenerative disorder characterized by multifarious dysfunctional alterations including mitochondrial impairment. In the present study, the formation of inclusions caused by the mutation of huntingtin protein and its relationship with changes in energy metabolism and with pathological alterations were investigated both in transgenic and 3-nitropropionic acid-treated mouse models for HD. The HD and normal mice were characterized clinically; the affected brain regions were identified by immunohistochemistry and used for biochemical analysis of the ATP-producing systems in the cytosolic and the mitochondrial compartments. In both HD models, the activities of some glycolytic enzymes were somewhat higher. By contrast, the activity of glyceraldehyde-3-phosphate dehydrogenase was much lower in the affected region of the brain compared to that of the control. Paradoxically, at the system level, glucose conversion into lactate was enhanced in cytosolic extracts from the HD brain tissue, and the level of ATP was higher in the tissue itself. The paradox could be resolved by taking all the observed changes in glycolytic enzymes into account, ensuing an experiment-based detailed mathematical model of the glycolytic pathway. The mathematical modelling using the experimentally determined kinetic parameters of the individual enzymes and the well-established rate equations predicted the measured flux and concentrations in the case of the control. The same mathematical model with the experimentally determined altered V
    Original languageEnglish
    Pages (from-to)4740-4755
    JournalThe FEBS Journal
    Volume275
    DOIs
    Publication statusPublished - 2008

    Fingerprint

    Dive into the research topics of 'Increased glucose metabolism and atp level in brain tissue of Huntington's disease transgenic mice.'. Together they form a unique fingerprint.

    Cite this