Defective mitochondrial respiration, altered dNTP pools and reduced AP endonuclease 1 activity in peripheral blood mononuclear cells of Alzheimer's disease patients
| Autor: | Guido Keijzers, Maria Moreno-Villanueva, Thuan-Son T. Dinh, Scott Maynard, Åse Marie Hansen, Alexander Bürkle, Gunhild Waldemar, Lene Juel Rasmussen, Anne-Mette Hejl, Vilhelm A. Bohr, Claus Desler |
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| Předmět: |
Mitochondrial ROS
Male Aging DNA damage DNA repair Cell Respiration Mitochondrion bioenergetics Peripheral blood mononuclear cell AP endonuclease Adenosine Triphosphate Cognition Sex Factors Alzheimer Disease ddc:570 DNA-(Apurinic or Apyrimidinic Site) Lyase Humans AP site Aged reactive oxygen species Alzheimer's disease APE1 bioenergetics dNTP pools DNA repair mitochondria peripheral blood mononuclear cells reactive oxygen species biology Nucleotides DNA Breaks Age Factors Cell Biology Middle Aged Alzheimer's disease peripheral blood mononuclear cells Molecular biology DNA-(apurinic or apyrimidinic site) lyase Mitochondria dNTP pools Biochemistry APE1 Case-Control Studies biology.protein Leukocytes Mononuclear Female Energy Metabolism Biomarkers Research Paper |
| Zdroj: | Scopus-Elsevier Aging (Albany NY) University of Copenhagen |
| Popis: | AIMS: Accurate biomarkers for early diagnosis of Alzheimer's disease (AD) are badly needed. Recent reports suggest that dysfunctional mitochondria and DNA damage are associated with AD development. In this report, we measured various cellular parameters, related to mitochondrial bioenergetics and DNA damage, in peripheral blood mononuclear cells (PBMCs) of AD and control participants, for biomarker discovery.METHODS: PBMCs were isolated from 53 patients with AD of mild to moderate degree and 30 age-matched healthy controls. Tests were performed on the PBMCs from as many of these participants as possible. We measured glycolysis and mitochondrial respiration fluxes using the Seahorse Bioscience flux analyzer, mitochondrial ROS production using flow cytometry, dNTP levels by way of a DNA polymerization assay, DNA strand breaks using the Fluorometric detection of Alkaline DNA Unwinding (FADU) assay, and APE1 incision activity (in cell lysates) on a DNA substrate containing an AP site (to estimate DNA repair efficiency).RESULTS: In the PBMCs of AD patients, we found reduced basal mitochondrial oxygen consumption, reduced proton leak, higher dATP level, and lower AP endonuclease 1 activity, depending on adjustments for gender and/or age. CONCLUSIONS: This study reveals impaired mitochondrial respiration, altered dNTP pools and reduced DNA repair activity in PBMCs of AD patients, thus suggesting that these biochemical activities may be useful as biomarkers for AD. published |
| Databáze: | OpenAIRE |
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